The Scientific Observer Issue 37

How To Navigate the Transition From PhD to Postdoc Unveiling the Progress and Challenges in the Fight Against HIV ISSUE 37, AUGUST 2024 2 CONTENT FROM THE NEWSROOM 04 ARTICLE “This Podcast Will Kill You” Hosts Talk Successful Science Communication, Overcoming Failure and Quarantinis 06 Molly Coddington ARTICLE How To Navigate the Transition From PhD to Postdoc 12 Andy Stapleton, PhD RESEARCH SPOTLIGHT Using Wearable Technology To Predict Cognitive Function in Patients With MCI 14 Suhanee Mitragotri ARTICLE Epstein-Barr Virus, Multiple Sclerosis and Cancer: Looking Back at 60 Years of Research 17 Blake Forman FEATURED ARTICLE Can We Prevent Immune System Aging? 20 Kate Harrison, PhD ARTICLE Chasing Dreams, Overcoming Obstacles and Making a Difference in the World of Medicine and Science 24 Karen Steward, PhD ARTICLE Unveiling the Progress and Challenges in the Fight Against HIV 27 Kate Robinson ARTICLE How Long COVID Research Could Change the Way We Think About Blood Microclots 31 Leo Bear-McGuinness ARTICLE Scientific Publishing Coalition Sees Purpose Lead the Way 35 Karen Steward, PhD MEET THE INTERVIEWEES 37 14 27 20 FEATURE Can We Prevent Immune System Aging? Kate Harrison, PhD AnnaMaria Vasco, iStock Dear readers, Welcome, to issue 37 of The Scientific Observer. In this issue, we bring together a diverse array of articles and interviews that highlight groundbreaking research in infection and immunity, kicking off with an exclusive interview with the hosts of “This Podcast Will Kill You”, Drs. Erin Welsh and Erin Allmann Updyke. The dynamic science comms duo shared a longing to talk about epidemics and bizarre medical mysteries in a way that was fun, relatable and helpful for everyone, regardless of their background. Speaking to Technology Networks, they discuss how their podcast was born and why infectious disease research is so fascinating. At the heart of this issue is our feature article, which sees Dr. Kate Harrison confront the topic of aging research from a unique angle – the immune system. As we age, so does our immune system. It remodels and, as a result, its ability to mount a robust immune response is hindered. Harrison explores how this process happens, how it can increase our disease susceptibility and interviews renowned experts to learn whether we can stop it. Also in issue 37, we spotlight innovative research, such as using wearable technology to predict cognitive function in patients with mild cognitive impairment, and take a retrospective look at 60 years of research on the Epstein-Barr virus, its connection to multiple sclerosis and cancer. Kate Robinson examines the ongoing battle against HIV, shedding light on progress and the challenges that remain, while Drs. Karen Steward and Andy Stapleton address wider issues in scientific research, such as scientific publishing coalitions and how to thrive in your transition from PhD to Post-Doc. We hope you enjoy this issue and, as always, thank you for reading. The Technology Networks Editorial Team 3 Kate Harrison, PhD Kate is a Senior Science Writer at Technology Networks. Kate Robinson Kate is a Science Editor for Technology Networks. EDITORS’ NOTE CONTRIBUTORS Blake Forman Blake is a Senior Science Writer for Technology Networks. Andrew (Andy) Stapleton, PhD Andy Stapleton is an educator, entrepreneur and research chemist. Karen Steward, PhD Karen is a Senior Scientific Specialist for Technology Networks. Leo Bear-McGuiness Leo is a Science Writer for Technology Networks. Molly Coddington Molly is a Senior Writer and Newsroom Team Lead for Technology Networks. Suhanee Mitragotri Suhanee is an undergraduate student at Harvard University and a freelance science writer. 4 iStock, Meixiang Wang/ NC State University Want to learn more? Check out theTechnology Networks newsroom. Older individuals who self-reported using psychedelics had fewer depressive symptoms and higher cognitive performance. Older Psychedelic Users Report Fewer Depressive Symptoms MOLLY CODDINGTON The drug donanemab (also known as Kisunla™) has been approved by the US Food and Drug Administration (FDA) for the treatment of adults with early symptomatic Alzheimer’s disease (AD). This marks the second anti-amyloid antibody given full FDA approval to slow the progression of the disease. New Alzheimer’s Drug Donanemab Approved by FDA SARAH WHELAN Researchers have developed a new class of materials that perfectly blend the hardness of glass with the stretchiness of gels. These “glassy gels” could have future applications in 3D printing, batteries and soft robotics, according to the creators of the new polymer class. Researchers Create “Glassy Gels”, A New Class of Materials ALEXANDER BEADLE 4 FROM THE NEWSROOM From the Newsroom 5 iStock, Mosconi Lab From the Newsroom 5 FROM THE NEWSROOM Want to learn more? Check out theTechnology Networks newsroom. Reducing intake of processed meat products like bacon, salami and corned beef by a third could prevent more than 350,000 cases of diabetes in the US over 10 years, according to researchers from the University of Edinburgh. To Prevent Diabetes and Colorectal Cancer, Americans Could Cut Down on Processed Meat, Say Researchers LEO BEAR-MCGUINNESS Nightmares and hallucinations could be early warning signs of autoimmune diseases. Many of these neuropsychiatric symptoms haven’t been explored before and the researchers argue that there needs to be greater recognition that mental health symptoms can act as early warning signs of autoimmune disease. Nightmares and Hallucinations Could Be an Early Sign of Autoimmune Disease BLAKE FORMAN Menopause is associated with neuropsychiatric symptoms such as brain fog and depression. 17β-estradiol (E2) is the most biologically active form of estrogen and previous research has highlighted its role in various neurological and cognitive functions. In Vivo Imaging Reveals Increased Estrogen Receptors in the PostMenopausal Brain RHIANNA-LILY SMITH 6 Dr. Erin Welsh and Dr. Erin Allmann Updyke describe themselves as a “one-two punch of infectious disease knowledge”. The sci-com world’s iconic duo formed a friendship during their PhDs at the University of Illinois at Urbana-Champaign, where Welsh studied disease ecology and Allmann Updyke studied disease epidemiology. It’s no secret that discussions of science – be it through journals, conferences or lab meetings – can be somewhat intense, often loaded with complexity and jargon. The Erins shared a longing to talk about epidemics and bizarre medical mysteries in a way that was fun, relatable and helpful for everyone, regardless of their background. While exchanging podcast recommendations with one another, they stumbled upon the idea of launching their own and, before long, “This Podcast Will Kill You” (TPWKY) was born. Since 2017, the Erins have taken listeners on a weekly deep dive into a disease, exploring its biology, history, epidemiology and how it has affected the world. The podcast’s archive features episodes on some of the world’s weirdest and (not so) wonderful pathogens, as well as disorders such as endometriosis and Parkinson’s. Each episode kicks off with a firsthand account of someone impacted by a disease, em- “This Podcast Will Kill You” Hosts Talk Successful Science Communication, Overcoming Failure and Quarantinis MOLLY CODDINGTON Grant Czadzeck, Erin Welsh and Erin Allmann Updyke DR. ERIN WELSH AND DR. ERIN ALLMANN UPDYKE. 7 phasizing the human element of the science that is discussed afterward. Instead of lecturing their audience, the Erins approach each podcast episode as an opportunity to teach and learn from one another. This refreshing approach to science communication has resonated with listeners both within and outside of the scientific community; at the time of writing, 147 episodes are available and boast rave reviews. TPWKY has also been recognized through Webby Award nominations in the Science and Education Podcasts category. In this interview, they reflect on their journey so far, sharing how they built TPWKY and offering advice for budding sci-commers. They also explain the origin of the famous “quarantini”. Molly Coddington (MC): What interested you so much about infectious disease research, and why did you choose to pursue a career in this field? Erin Welsh (EW): It was a roundabout journey for me that always had a destination, but I didn’t know what I wanted to research along the way. I started my undergraduate studies in nursing where I took a microbiology class and thought, “Hey, I really want to be in this class”. I didn’t want to sleep through my alarm; I wanted to get up, hop on my bike and get there for the 8am start. This was a little unusual for me. I changed my major to biology and joined a research lab studying the plague bacterium Yersinia pestis, which was very cool. That’s where a taste for the historical analysis of epidemics started to emerge. When I joined the lab, the first thing I did was head to the library and find a book all about the Black Death – I wanted to know everything about it. From then on, this would become my “fun time” exploration of disease. My academic work was focused on the bacteria themselves, and I found myself thinking that this was such a small view of what I was interested in within infectious diseases. I decided to pursue a master’s degree in epidemiology and, when I was getting ready to finish that degree, one of my committee members asked what my next step was. I said that I would probably do a PhD in epidemiology when he suggested I consider ecology. A large part of my thesis had explored environmental influences on parasites, but it never occurred to me that this was something I could study. Erin Allmann Updyke (EAU): Similar to Erin, I had never intended to work within disease. I was studying marine biology and then took an ecological parasitology class, and that’s what shifted my mindset to one of “Okay, so these parasites are my people”. I needed to know more about them. I went on to do a master's degree in public health and thought that I wanted to be involved in outbreak investigation work. I completed my PhD in entomology and that’s where I met Erin – we were in the same laboratory. It’s interesting to look back over how this journey has progressed, because so much of the work that we do now is focused on trying to break things down in a way that anyone, regardless of their background, can understand and appreciate. They can appreciate not only how fascinating these diseases are, but how big of an impact they have on society and our planet. Throughout my education, so much of the work that I enjoyed doing was of a similar theme, such as informal education work in undergrad studies. It feels as though everything has come together. MC: You describe feeling “disenchanted with the insular world of academia”. Can you talk about how this manifested for you? Was there a specific moment or event that led to the creation of TPWKY? EAU: We both finished our PhDs in 2018, and so in the summer of 2017 we were attending a lot of different conferences. Conferences can be incredible – you learn so much from the fascinating research that is being presented and you get to connect with lots of different people. But as the end of our PhDs were approaching, we found ourselves asking “When is this going to go beyond just these four walls?”, or however many walls the conference hall had! We had both gotten really interested in public health because of the impact that diseases and disease ecology have on such a large scale. I wanted to be able to reach people that might never be at one of these conferences, but still wanted to know about this research. Me and Erin were being antisocial at a barbecue towards the end of summer – a normal habit for us – when we started discussing the podcasts that we both listened to. We had this eureka moment where we knew we needed to start a podcast about disease, because nothing like that existed and it could be a cool thing. That was really the moment when TPWKY was born. EW: We had also become tired of the impersonal language so often used when discussing science. We wanted it to be fun and engaging and exciting. We had missed talking about research topics such as the origin story of the Despite the challenges that can accompany a career in science communication, the Erins have persisted in building a platform that educates and inspires people all across the world. 8 Exactly Right nickname “clap” for gonorrhea, or the fact that rabbits can have growths caused by the Shope papilloma virus, which may have inspired the mythical Jackalope creature. These fun tidbits are so interesting, and you aren’t always able to explore as much as you’d like when you’re deep into PhD studies. We loved talking about science and wanted to have a fun, relaxed outlet for doing so. I don’t think we realized that so many other people would feel the same way. TPWKY has been one of the greatest joys from that respect. MC: Please can you describe everything that our readers need to know about the podcast – including the “quarantinis”? EW: TPWKY is the science podcast that explores the biology, history and current status of various diseases and other medical topics. But of course, there's a lot more to it than just that! At the beginning of each episode, we include a firsthand account, often from someone who has direct experience with the disease. We have done this from the very beginning in order to humanize the topic that we’re talking about, and as a way to complement learning about the biology of the disease. Take the plague for instance. When you learn about plague in a classroom setting, you’re probably learning about whether it’s a gramme positive or negative bacteria, what it looks like on a stain, what its symptoms are or how long the incubation period is, etc. This is the nitty gritty of science. But if you learn about it from a historical perspective, you also get to explore the impact it had on the economic structure of major parts of Europe or learn how it shifted the primary language to English after the decline of French and Latin. You might learn about the invention of quarantine. When we started the podcast, we wanted to be able to look at a disease from all different perspectives and then relate it back to the human aspect that this firsthand account provided. Then there’s the “quarantini”. This was just a way for us to have fun, and for people to know that this is not a serious podcast – or at least not all of the time. We make a themed cocktail for each episode of the podcast, which now includes alcohol free versions, the “placeboritas”. Over time we’ve created cocktails such as the “hair of the rabid dog”, “smallpox on the rocks” and many others. Our gonorrhea episode featured a cocktail called “burning love” – it’s really delicious. We had both gotten really interested in public health because of the impact that diseases and disease ecology have on such a large scale. I wanted to be able to reach people that might never be at one of these conferences, but still wanted to know about this research. MC: Sometimes the scientific environment can feel like an intimidating place. There can be a lot of doubt – particularly in young scientists – about whether they belong there. You both make science feel welcoming and a place for everyone. Can you talk about how do you do this? EAU: It’s very intentional, and it’s something that can be quite challenging to balance because we never want to sugarcoat or present anything that’s incorrect. We want to present information in a way that is logical and easy to follow. This feels particularly important for the historical aspect of the podcast, at least for me. I was a “science kid” – I knew nothing about history. Now, my favorite part of the podcast is being able to learn about something that I’m really interested in, in a way that is really interesting. No matter what your background – whether it’s science-heavy, history-heavy or neither – there’s still something that you can get out of the podcast. MC: What is the most enjoyable aspect of creating TPWKY? EAU: I have two favorite parts. The first is that I get to work with Erin. It’s perhaps a cheesy answer but it’s true – we started this process just being best friends. I love being able to work 9 Abigail E. Penner with her, to learn from her and the fact that we have maintained our friendship throughout this whole process. My second favorite part is that we have reached people in a way that I never thought would be possible. We receive emails from listeners that have gone back to school after listening to the podcast or got their flu jab for the first time. It’s incredible to have had that impact on people’s lives. EW: I think Erin hit the nail on the head. I also love that this podcast gives me the opportunity to learn broadly across different fields rather than just intensely in one. Being able to follow a line of curiosity down a rabbit hole and not being restricted in terms of it being “relevant” to your work. MC: Have you experienced any “failures” in your careers thus far? If so, what did it teach you? EW: After finishing my PhD, I went on to do a postdoc in Finland, and I left that postdoc early. I am no longer involved in academia. I think that, when you are trained in graduate school, you are trained to be an academic – period. You are not trained to work in any other industry unless you seek that training elsewhere. Leaving academia, even though I knew without a doubt that I did not want to be in that world, felt like a failure. I had spent years of my life doing something that was not what I would end up doing. Now, with distance and time, and being able to do the thing that I truly love and I am fulfilled by, the feeling that this was a failure has started to ease. It was my choice, and my reasons for doing so were valid. Often it’s seen as a problem when someone leaves academia, rather than the conversation being centered around academia itself. I think that this really needs to get revisited. EAU: I remember a lot of small failures throughout grad school; I could never, ever keep a cell culture line alive – I just wasn’t physically capable of it! Pretty much all of the grants and fellowships that I applied for, I never got. I never published 98% of my PhD thesis, and I still feel a little guilty about that. So, there's a lot of small failures, and then there are bigger ones. I echo what Erin has said. I am still in training right now, in the last year of my residency. Even today, every single person asks me: what are your plans for the future? I still don't have an answer for them. Besides that, I want to do the podcast, but because it’s not academia or it’s not straight medicine, I feel a sense of guilt in saying that, which I think is just so unfair – I know how hard we both work, and the impact the podcast has had. But it’s a nontraditional career path, and that can sometimes come with stigma attached to it. Science is just failing over and over and over again until you figure something out. Having the mindset of “it’s okay to fail”, because that’s the only way that we learn, is important. I have failures, but I don’t have regrets. MC: What advice would you offer others who would like to become science communicators? EW: As I’ve had no formal training, it's like hard to articulate, but I think one of the most important aspects is just trying out different things and doing it, instead of seeking perfection before you start. You have to feel happy with what you’re sending out to the world, but it doesn't have to be perfect. I think Erin and I both had the hardest time working on the episodes that we had the most knowledge about, because when you're overexposed to something you forget the building blocks of knowledge that are required to understand it. So, I think that it’s important to practice science communication by talking with people who are not scientists about it. Ask I was always asked what I wanted to do when I got older when I was a child, and my answer was always to read books. I literally get to do that now! 10 them to repeat back what you just told them, to see if they’re able to articulate it, to find out what they struggled to interpret, etc. Now, with distance and time, and being able to do the thing that I truly love and I am fulfilled by, the feeling that this was a failure has started to ease. It was my choice, and my reasons for doing so were valid. Often it’s seen as a problem when someone leaves academia, rather than the conversation being centered around academia itself. I think that this really needs to get revisited. EAU: I definitely echo Erin here – just do it. When people train for a career and then consider that it might not be for them anymore, the hardest part is always just taking that leap and actually doing the thing they want to try. It can be really hard and scary because you might fail. My second piece of advice would be to find something that you are actually passionate about and have fun doing. Work isn’t always fun – making our podcast still requires a lot of work! Don’t get me wrong, there are days when we’re like “We don’t want to record this episode”. But, on the whole, I think that what makes us effective as science communicators is that we want to be doing this. Interest and passion go a really long way. MC: What’s the greatest thing about being women in science? EW: Usually the question is “What is the most challenging thing about being a woman in science?”, so I had to really think about this one. I asked my group chat that is full of women that went to the same school as me and Erin. We all have different careers now; some of us are in industry, some of us are physicians and some of us are science communicators. They responded with answers such as “getting to inspire the next generation of scientists”, or “being able to pursue something that you never thought you would do as a kid”. Then somebody pointed out that we are all in this group chat together, all women scientists, all supporting each other and understanding what we’re going through. Even if we aren’t having the same experience as each other, we can still relate, empathize or sympathize. That is really the best thing about being part of this amazing community. The fact that I was able to ask a group of women, who have all kept in touch over the years, and getting amazing answers; well, I think that’s the best thing about being a woman in science. EAU: I feel exactly the same. When Erin asked that question in our group chat, I was like, this really is the best part – the community that exists around being women in science. I think it's knowing that there is always somebody that you can talk to, that's going to have your back and that’s going to understand and support you. ⚫ thispodcastwillkillyou Instagram 11 EDITORS’ NOTE CONTRIBUTORS Have an idea for a story? If you would like to contribute to The Scientific Observer, please feel free to email our friendly editorial team. Giving talks and posters at conferences can be great but can also be expensive and time consuming. Your reach is also limited to the people in the room. What if you could get your paper in front of 250,000 scientists located across the globe, without leaving your desk, for free and with minimal work? Sound too good to be true? Find out more NEED TO DISSEMINATE YOUR RESEARCH? We want to help connect scientists with great research and have created an easyto-complete form and guidance to help distil the essence of your paper into a short, punchy article that will then be shared: on our site, which receives over 1 million page views every month with our 4 million + social media followers in our 18 newsletters and may be included in our regular digital magazine The Scientific Observer 12 iStock E scaping the confines of a PhD can be one of the most challenging and transformative periods in an academic career. Suddenly, you're a newly minted Dr., and the world seems ripe with opportunities. But is it as exhilarating as it sounds? Reality often paints a different picture. In this article, we delve into the emotional and psychological evolution from PhD to postdoc, exploring the vital steps needed to rebuild your identity beyond academia. Whether you're grappling with the shift to a structured workday or seeking strategies for long-term academic success, you’ll find practical advice and personal anecdotes to help you thrive in your postdoc journey. THE EMOTIONAL AND PSYCHOLOGICAL EVOLUTION Make no mistake, one of the biggest changes people face when transitioning from PhD to postdoc is how they feel about themselves. You are now a Dr.! Surely, it would feel amazing…right? Well, no. Post-PhD depression is a real and common experience for many new graduates. Engaging in activities outside of academia allows you to rediscover and develop personal interests that may have been sidelined during the intense focus of your university years. For instance, I immersed myself in community-driven hobbies like drumming in a Brazilian percussion group which proved crucial in helping me overcome post-PhD depression. These activities not only provided a much-needed break from academic pressures, but also offered a sense of belonging and joy that was so important in making my postdoc life better. It's important for newly graduated PhDs to recognize these emotions as normal and seek support through counseling, peer groups or mentors who understand the unique challenges of this transition. Many PhD students forget that their identity extends beyond their research project, and the project's completion often leaves a cold void that can go unrecognized for what it is – a form of grief for the loss of your identity. Rebuilding other facets of your identity and nurturing your hobbies is a crucial step to take after completing your PhD. ADAPTING TO A NEW RESEARCH ENVIRONMENT As a postdoc, you’ll likely have new project or admin management responsibilities that you didn’t have as a PhD student. This could include managing team members and ensuring project deliverables. It might involve supervising junior researchers, coordinating collaborative efforts and ensuring that project milestones are met on time. Developing strong communication and organiHow To Navigate the Transition From PhD to Postdoc ANDY STAPLETON, PhD 13 zational skills is crucial for effectively managing these responsibilities and creating a productive research environment for yourself. One effective solution to handle these new challenges is to seek out training and resources in project management and leadership. I enrolled in my university's mentoring program and found it incredibly rewarding. I highly recommend seeking out mentors to help you navigate this transition. Often, younger academic staff members can provide more relevant guidance and support than more established academics. Also, it can be tough adjusting to a structured, job-like environment after the haphazard timetables of a PhD student. During a PhD, students often have flexible schedules, allowing for periods of intense work followed by downtime. In contrast, I found that all of my postdoc positions typically required adherence to more regular working hours and consistent productivity. This shift can be challenging, but also offers an opportunity to develop a more balanced and sustainable work routine. I was fortunate that the research group I joined had a strong industry influence, making it common for people to work a standard nineto-five day. However, I recognize this isn’t always the case. Establishing a clear schedule and setting boundaries between work and personal time can significantly aid in adapting to this new environment. CAREER DEVELOPMENT AND LONG-TERM PLANNING If you want a career in academia, it is important to see the postdoc years as an opportunity to increase your publication record. Don’t do what I did, which was assume that this was just the next step in the inevitable path to an academic career – I didn’t push enough for publications, and I paid the price for it. Building a strong publication record is essential for securing future academic positions and grants. Postdocs should prioritize writing and submitting papers, collaborating with colleagues on publications, and taking advantage of opportunities to present their work at conferences. This proactive approach to publishing will enhance your academic profile and open doors for future career opportunities. Come up with a plan for transitioning from being employed on someone else’s grant to becoming an independent researcher – developing a clear plan for transitioning to an independent research career is crucial for longterm success. This includes identifying potential funding sources, understanding the application process, application timelines and building a compelling research proposal. One thing you should be aiming for is to build a network for collaborations and future opportunities. Networking is a vital component of academic success, and postdocs should actively seek out opportunities to collaborate with researchers both within and outside their institutions. Attending conferences, participating in academic societies and engaging with online research communities can help you build a network of contacts who can provide support, advice and collaboration opportunities. A strong professional network will enhance your research, increase your visibility in the academic community and open doors for future career opportunities. EMBRACING THE POSTDOC JOURNEY As you navigate this new territory, it's essential to recognize the emotional and psychological shifts that come with it. Remember, feeling a sense of loss after completing your PhD is normal, but it's crucial to rebuild your identity by engaging in activities outside of academia and seeking support from mentors and peers. The post-doc journey is about finding balance, honing your skills and preparing for the next stage of your academic career. By recognizing and addressing the challenges, you can turn this period into a rewarding and enriching experience. ⚫ Many institutions offer workshops, courses or seminars specifically designed for early-career researchers. iStock Using Wearable Technology To Predict Cognitive Function in Patients With MCI Suhanee Mitragotri RESEARCH SPOTLIGHT Mild cognitive impairment (MCI), a decline in an individual’s cognitive function that is greater than what would occur due to aging alone, impacts over 15% of older adults worldwide. A multi-institutional study, led by Dr. Yuri Rykov at Neuroglee Therapeutics and published in BMC Medicine, demonstrates the potential of using wearable technology to predict cognitive function in patients with MCI via physiological markers. iStock 14 Research Spotlight LACK OF MONITORING FOR PATIENTS WITH MCI MCI is characterized by frequent lapses in thinking or memory during routine activities, which can manifest as consistently forgetting important people or events, struggling to maintain coherent thoughts and misplacing items on a regular basis. MCI often serves as a precursor for more severe conditions, such as Alzheimer’s disease and dementia. Traditional neuropsychologist tests for patients with MCI only capture clinical data during doctor visits, leaving gaps in data when the patients are not at the clinic. Wearable sensors, such as Fitbit, are already capable of collecting information including blood volume pulse, which can be used to calculate heart rate and heart rate variability (HRV). Previous research studies have shown a correlation between HRV metrics and cognitive function, specifically in executive function and episodic memory. Dr. Rykov’s team built on this research through this study in which they tested the ability of wearable sensors to predict cognitive function as a method to provide continuous monitoring of patients with MCI. USING WEARABLE TECHNOLOGY TO PREDICT COGNITIVE FUNCTION The 10-week clinical trial was designed for older adults, aged 50–70, including 30 individuals diagnosed with amnestic MCI and 10 age-matched cognitively normal individuals. During the trial, participants underwent regular digitally delivered multidomain therapeutic intervention sessions. They were asked to wear the Empatica E4 wrist-wearable device during these sessions, as well as during sleep and other routine activities. Cognitive performance was measured at baseline at the start of the trial and again at the end of the 10 weeks using the neuropsychological battery test (NTB), which includes assessments of executive function, processing speed, immediate memory, delayed memory and global cognition. The device recorded physiological data, such as blood volume pulse, electrodermal activity, acceleration and skin temperature. They utilized supervised machine learning to train models predicting NTB scores using digital physiological features and demographics. Out of the 30 individuals diagnosed with amnestic MCI, 27 completed the trial, and 7 out of the 10 controls completed the trial, with missing data being attributed to improper device usage or non-compliance. The key findings from this study were that: • Digital physiological features showed strong correlations with processing speed, executive function and global cognition composite scores. • Measures of HRV, particularly cardiac sympathetic index (CSI) and the high frequency HRV (HRV-HF), correlated significantly with the cognitive composites. • Predictive models that combined digital physiological features and demographics demonstrated the greatest predictability for executive function scores. THE POTENTIAL OF WEARABLE TECHNOLOGY FOR CONTINUOUS COGNITIVE MONITORING The research team found significant correlations between tracked physiological markers and key cognitive aspects such as processing speed, executive function and overall cognitive performance. These components of cognition are essential for everyday cognitive tasks, underscoring the potential of wearables for continuous monitoring of cognitive function in patients with MCI. HRV measures, in particular, showed promise in predicting cognitive performance. Continuous monitoring offers clinicians a convenient way to gather patient data outside of the clinic. This can be especially advantageous after the implementation of a new treatment protocol or during periods of significant deterioration in patient health because it can fill in missing data gaps that would otherwise exist. If a patient were to come into the clinic with severe deterioration in cognitive function, physicians would have the ability to track changes specifically by looking at data from wearable sensors, which could help them point to a particular time or date at which these changes occurred. Nevertheless, this study had limitations that could have impacted the findings. Firstly, the sample size is relatively small, with no control group that did not receive the intervention, and non-compliance led to the loss of potential data that could have contributed to the study. Specifically, only data from 17 individuals was viable to use after data cleanup. Secondly, the study period was relatively short, so long-term effects may have been missed. Additionally, given the setup of the study, factors such as the amount of physical activity or daily routine were not controlled for, which could have impacted the results, especially since many of the physiological markers, such as heart rate data, can easily be influenced by external factors. Furthermore, the study sample displayed a lack of ethnic variation, which makes the results less generalizable to a larger population. DEVELOPING A MORE CONTROLLED STUDY Further research is needed to control for more external factors and ensure that these markers are reliable predictors of cognitive function. Moreover, a controlled study would allow for greater exploration of potential confounding variables, thereby enhancing the validity and generalizability of the findings. The authors acknowledge that the achieved accuracy of the predictive models is currently below desirable levels, preventing the replacement of standardized cognitive tests with wearable-based physiological measurements as they are. However, with further work, this approach shows promise for improving care for patients with MCI. ⚫ RESEARCH SPOTLIGHT 15 This online event is aimed at those working within academia and pharmaceutical drug development, who want to hear from experts across their field. Focus will be given to the latest advances in small molecule drug discovery and development, biopharma and biotechnology. REGISTER NOW Brought to you by the publication September 18–19 2024 8AM PDT | 11AM EDT | 4PM GMT SPEAKERS Joseph Tucker, PhD Enveric Biosciences Inc Adityo Prakash Verseon Raviv Pryluk, PhD PhaseV Melanie Homberg, PhD Lonza Aurita Menezes, PhD Lonza Sharmeen Roy DoseMe Romina Durigon, PhD Sphere Fluidics Niven Narain, PhD BPGbio Jamie Spangler, PhD John Hopkins University Kevin Grady Lonza Steffen Grimm Evotec Annie Yim, PhD Boehringer Ingelheim Franziska Hausig-Punke, PhD Analytik Jena Jon Stokes, PhD McMaster University STANDARD SPONSORS PLATINUM SPONSOR TECHNOLOGY SPOTLIGHT SPONSORS Advances in Drug Discovery & Development ONLINE SYMPOSIUM PANEL DISCUSSION 17 iStock T he Epstein-Barr virus (EBV) was the first virus to be discovered that could cause human cancer. Since then, the virus has been implicated in the development of a range of different cancers and, more recently, in the development of multiple sclerosis (MS). Studying EBV over the past 60 years has shed light on general aspects of cancer pathogenesis, the immunology of virus infections and different approaches to cancer immunotherapy. Lawrence Young is an emeritus professor of molecular oncology and director of the Warwick Cancer Research Centre at the University of Warwick. Known for his work on the role of virus infection in the development of cancer, his research has led to several clinical trials including contributing to the ongoing development of a therapeutic EBV vaccine for MS. In an interview with Technology Networks, Young discusses the historic discovery of EBV, the current interest in EBV vaccines and his thoughts on the future direction of virology research. Blake Forman (BF): For our readers, who may not be familiar with the discovery of EBV, can you elaborate on the historical journey of EBV discovery and how it was first linked to cancer? Lawrence Young (LY): During the 1950s, a young pathologist called Anthony Epstein was investigating the Rous sarcoma virus, a virus that was known to cause cancer in chickens. Epstein was interested in understanding if viruses could also play a role in human cancer. In 1961, Epstein attended a lecture by Denis Burkitt, a surgeon working in Africa. Burkitt had discovered a lymphoma that appeared in the jaws of young children. He mapped the appearance of this lymphoma to areas where malaria was common. This sparked interest in Epstein who hypothesized that an infectious agent may be the cause of this lymphoma. Following the lecture, Burkitt arranged to send tumor samples from Africa to London for Epstein to investigate further. After a few years of trying in vain to find a virus in the samples, Epstein, alongside a young researcher called Epstein-Barr Virus, Multiple Sclerosis and Cancer: Looking Back at 60 Years of Research BLAKE FORMAN 60 YEARS ON FROM THE DISCOVERY OF THE EPSTEIN-BARR VIRUS, PROFESSOR LAWRENCE YOUNG DISCUSSES CURRENT EFFORTS TO FIND A VACCINE. 18 Yvonne Barr, was eventually able to grow free-floating cancer cells to study. BF: Given the significant role of viruses in cancer development, why do you think public awareness about this link remains limited? LY: Cancer-causing viruses are responsible for approximately 30% of cancer cases in low- and lower-middle–income countries and around 15% of cancers worldwide. Given the amount of research in this area and its applications in human health, it is surprising there is not more public awareness. Studies into the role of viruses in cancer have led to the development of vaccines as with the human papillomavirus. Similarly, a vaccine against hepatitis B has been used to help prevent the development of liver cancer for quite some time. I think the limited public awareness of the role of viruses in cancer comes down to a lack of publicity. BF: Can you talk about the current interest in EBV vaccines; what impact could these vaccines have on the management of associated diseases such as MS? LY: The development of vaccines against EBV has had a somewhat checkered history. One of the problems is that more than 90% of adults globally are infected with this virus. Often, we contract the virus when we are young and there are no symptoms. Stopping the early transmission of the virus is very difficult. Individuals who contract EBV as adults are much more likely to develop glandular fever, otherwise known as infectious mononucleosis. There has been a lot of work over the years to try and develop vaccines that might prevent this disease. This has been difficult to justify economically because of the relatively small number of people who get glandular fever. You would also ideally need to vaccinate all individuals as babies, probably at birth. There is renewed interest in an EBV vaccine off the back of studies identifying EBV as a driving force in the origin and development of MS. We've learned a lot more about the different proteins that the virus produces to get into different cell types. This has made researchers more aware of the fact that if we're going to have an effective vaccine, we're going to have to use a combination of different EBV proteins as targets. The revolution in our understanding of vaccinology, particularly as it relates to mRNA vaccines, means that we can incorporate many more elements of a virus into a vaccine. Something that we know has been very important during the COVID-19 pandemic. Moderna is currently involved in early clinical trials looking at an mRNA vaccine for preventing EBV infection. There is hope that vaccines like this could be used not only to prevent EBV-associated diseases like MS but also to treat people with these diseases including cancer. BF: Are there any current hurdles in the study of EBV? LY: There is a current lack of funding for fundamental research and there is still a lot we need to learn about the virology of EBV and similar viruses. The focus is now on developing better approaches to treating EBV-associated malignancies. That shift is understandable when resources are limited, but one concern I have is that we still need to fund basic virology. Due to COVID-19 people are now more aware that we must not be complacent about viruses. I would hope that some of that would translate into more funding for fundamental research into virology. BF: Are there any novel technologies or methodologies that you think will help progress studies further? LY: It has been difficult to manipulate the viral genome of EBV due to its large size. We've now got much better With the help of a colleague called Burt Achong, and by studying Burkitt’s lymphoma cells with an electron microscope, the researchers were able to identify virus particles that looked like the shape of a herpes virus in the growing cancer cells. In 1965 the scientific community confirmed that Epstein and company had spotted a brand-new human virus, and it was officially christened Epstein-Barr virus. 19 iStock methodologies for studying genomes of this size. This means that we can now make recombinant forms of EBV so that we can study the function of individual virus genes in the context of the whole virus. Separating viral DNA from human DNA to sequence it has also been challenging but new technology is now providing us with better ways of doing this. EBV was first sequenced in 1984, which was when I first started in the field. At that time, it was the largest piece of DNA ever sequenced. We now have access to better techniques that are helping us determine whether there are different varieties of EBV. We know there is some variation (polymorphisms) in the EBV genome. Studying this further will help us understand if there is a specific variant of EBV that might be more associated with MS. BF: How do you envision EBV research evolving in the next few years? LY: EBV research has led the way in the development of early diagnostics for cancer. Measuring EBV DNA in the blood is a good indicator when investigating if an individual might go on to develop EBV-associated cancer. Alternatively, when an individual has EBV-associated cancer, measuring EBV DNA levels in the blood can tell you whether they're responding well to therapy and if the cancer recurs. More generally, studying tumor DNA in the blood as a liquid biopsy for cancer is an exciting and expanding area of research. Understanding the virus at the epidemiological level is another continuing avenue of investigation. Some of the most common EBV-associated malignancies occur in specific parts of the world. For example, EBV-associated nasopharyngeal cancers are particularly common within the Chinese population. Further research is still needed to understand why this is. A combination of the underlying genetics of the individual, environmental factors and the genetics of the virus itself may contribute. All monkeys have a version of EBV so it may have helped our immune systems to develop from an evolutionary perspective. One of the big questions is: if you completely eradicated EBV from your body, would it mean you are more susceptible to other infections? There is evidence, for instance, that EBV is important as we get older in that it helps tweak our immune system. One interesting aspect that hasn’t been studied enough is understanding why a small percentage of people don’t ever contract EBV. Is there anything different about them in terms of their susceptibility to disease or other diseases that could be harnessed? Studies have demonstrated that when individuals are infected with SARS-CoV-2, EBV reactivates, and replication increases. A proportion of individuals with long COVID appear to have more EBV floating around in their bodies.5 This is interesting as there has been a long history of EBV and its potential role in chronic fatigue syndrome. Studying how EBV interacts with other viruses will also be vital to better understanding these conditions and to developing improved therapies. ⚫ 20 iStock Credit Line kate harrison, phd AnnaMaria Vasco 21 iStock The world’s population is aging rapidly – by 2050, 17% of people will be over 65, an estimated increase of almost ~100% from 2019. While this will have significant effects on multiple sectors of society, one of the most concerning impacts is the huge increase in demand for healthcare. As people age, their susceptibility to infection increases – as does the likelihood of poorer outcomes to infection. The idea of “healthy aging” – the ability to retain as much physical, mental and social ability as possible into old age – is therefore set to become a huge focus in aging research. “If you look at recent aging reports published by the House of Lords, there is a big gap between how long we are living and our actual health span,” says Dr. Niharika A Duggal, assistant professor in Immunity and Aging at the University of Birmingham, and trustee for the British Society of Research in Aging (BSRA). “The UK government is aiming to add an extra 5 years of good health within the average lifespan by 2035, but one of the key challenges obstructing this goal is immune aging and the increased risk of infections in those aged 75 and older.” However, extensive research efforts are underway, investigating both pharmacological and non-pharmacological interventions that could reverse – or at least slow down – immune system aging. Could we eventually turn back time on our failing immune systems? HALLMARKS OF IMMUNOSENESCENCE As the body ages, so too does the immune system. This immune aging results in a remodeling of the immune system and a reduced ability to mount a robust immune response, known as immunosenescence. Symptoms of immunosenescence include degradation of immune organs and a loss of new lymphocytes, coupled with a chronic proinflammatory state known as “inflammaging”. Together, these lead to the onset of age-related diseases, poor vaccination outcomes and increased susceptibility to infectious disease and malignancies. The effects of immunosenescence vary across both the innate and adaptive immune system, resulting in almost every component of the immune system displaying dysregulation of some form. Dysregulation begins with stem cells in the bone marrow, with reduced production of adaptive immune cells, but increased production of innate immune cells. Although this means that the numbers of most innate cells remain stable during aging, their ability to function normally can be significantly impacted. For example, aged neutrophils exhibit a reduced ability to migrate towards the site of infection, coupled with impaired pathogen killing. One particularly affected immune cell type is T cells. In addition to the reduction in overall numbers of new T cells produced by the bone marrow, changes in the thymus interfere with T-cell maturation, as this is the organ where T cells complete their development and become fully functional. “As you age, the thymus involutes, meaning it shrinks,” says Dr. Leen Slaets, assistant professor at Hasselt University, whose research focuses on protective interventions against immune aging. “In addition, the specialized thymic epithelium is replaced with adipose (fat) tissue, so the final steps of T-cell maturation will not occur as efficiently as in younger people.” This loss of new T cells means it’s much harder to fight off infections with new pathogens, which was nowhere more obvious than during the COVID-19 pandemic, when age was shown to be a significant risk factor for mortality. However, it isn’t just new immune cells that are affected by immune aging. In older adults, memory cells – i.e., cells that have already encountered a pathogen and can mount a faster, stronger response on a repeat encounter with the same pathogen – become the dominant T cell population, but these cells also show signs of immunosenescence. “When T cells become senescent, they start to lose expression of co-stimulatory receptors, that help them recognise pathogens,” explains Slaets. “They also become more inflammatory – for example, T helper cells start to produce the kind of cytotoxic molecules that are normally only produced by killer T cells.” WHAT DRIVES IMMUNE AGING? This shift towards a pro-inflammatory profile is echoed across the immune system. Senescent (aging) cells 22 occur in all areas of the body and are characterized by DNA damage and morphological, phenotypic and functional changes. They can become highly pro-inflammatory, contributing to an overall increase in base-level inflammation – a state known as inflammaging. Inflammaging not only alters the normal functions of the immune system, but can also increase the risk of chronic inflammatory and autoimmune diseases. One facet of Duggal’s research looks at the role of immunosenescence in the age-associated onset of chronic inflammatory diseases, such as rheumatoid arthritis (RA), and the drivers behind this increase in inflammation. “As we age, we begin to see a state of dysbiosis in the microbiome, which contributes to an increase in the permeability of the intestinal barrier, and transfer of microbial products into circulation,” she explains. “A 2017 study recognized dysbiosis as a causal factor in inflammaging. The hypothesis is that microbial products might induce this pro-inflammatory state due to chronic antigen stimulation, and their ability to skew T cells towards more pro-inflammatory subsets.” Immunosenescence can also drive aging in other organs and cell types. Studies in mice have shown that inducing targeted immunosenescence in young, otherwise healthy animals by deleting a DNA repair gene resulted in accelerated aging in other organs, including the liver and kidneys. These results demonstrated that the immune system plays a role in systemic aging, and suggest that improving immune function could contribute to improving health and wellbeing in older adults. SLOWING THE CLOCK: THE EFFECTS OF LIFESTYLE So, what can be done to mitigate immunosenescence, and boost the function of aging immune cells? According to research by both Duggal and Slaets, the answer may be simpler than first thought: diet and exercise. Duggal’s research group recently published a study that revealed older adults who adhered to a Mediterranean diet had fewer features of immunosenescence, such as accumulation of senescent T cells. “We think that the mechanism for this link lies in the microbiome,” she explains. “We’ve done a study in mice that shows that preventing transfer of microbial products from the gut into the blood stream also prevents build-up of adipose tissue and aging cells in the thymus. This means that we can possibly preserve the functions of the thymus and proper T-cell development.” Her group is now looking at similar trends in humans. “We can broadly classify our older adults into those that show dysbiosis and high levels of gut leakage (i.e., transfer of microbial products across the intestinal barrier), and those that show low levels, and we’re seeing more evidence of immune aging in those with high gut leakage,” she says. The protective effects of exercise against age-related diseases have long been established, however, exercise has also been shown to have direct ani-inflammatory and immunomodulatory impacts. “In cross-sectional studies, older adults who exercise regularly have lower numbers of senescent T cells and more new T cells that are still able to replicate well, compared to sedentary individuals,” says Slaets. Indeed, a study published by Duggal in 2018 showed that older adults who were avid cyclists exhibited higher levels of naïve T cells, immunoprotective elements and regulatory immune cells than their age-matched sedentary counterparts. However, the molecular mechanisms are still unclear. “In general, regular periods of moderate exercise, whether aerobic exercise or resistance training, are associated with reductions in inflammatory markers,” Slaets goes on to explain. “We hypothesize that the metabolites produced by the muscles help reduce immunosenescence; for example, skeletal muscle is a major source of the amino acid glutamine, which has been shown to improve T-cell proliferation.” Another theory suggests that exercise flushes immune cells – particularly T cells – from lymphoid tissue into circulation, increasing their opportunities to attack and eliminate pathogens and malignant cells, while also increasing the turnover of senescent cells. Dr Slaets’ lab is currently investigating the effects of biological sex on T-cell senescence during exercise intervention. BOOSTING IMMUNE FUNCTION: PHARMACEUTICAL INTERVENTIONS As simple as these interventions sound, diet and exercise changes are not possible for everyone, and in some contexts – such as vaccination – the aging immune system may still need a pharmaceutical helping hand. Dr. Jenna Bartley is an assistant professor at the Center of Aging, University of Connecticut, where her research focuses on boosting immune responses to vaccination in older adults. “When a younger person is vaccinated, we usually see a classical, textbook adaptive immune response,” she says. “But older adults have a reduced adaptive response, which means lower levels and a shorter duration of vaccine protection.” “Adipose tissue is a big source of inflammaging and pro-inflammatory, senescent cells, and it also contributes to thymic involution,” says Duggal. “So, reducing adipose tissue is linked to maintaining a healthy immune system.” 23 iStock Bartley’s research aims to improve vaccine responses in older adults, using specific pre-vaccination interventions. “A huge advantage for implementation would be to not need to reformulate vaccines, but rather give an intervention to an older adult prior to vaccination that would then induce a stronger, more youthful immune response.” Metformin is one such potential intervention. Metformin is the first line medication for type 2 diabetes. However, the drug also targets many of the hallmarks of aging, including reducing metabolic dysregulation in immune cells, inflammation and immunosenescence. “We showed that pre-treating older adults with metformin before influenza vaccination improves T helper cell responses,” she explains. Although this was only a pilot study, metformin has also been shown to significantly reduce the risk of hospitalization and mortality in COVID-19 and influenza infections in older and otherwise vulnerable populations. Another potential intervention is a class of drugs called senolytics, which target and kill senescent cells. Senescent cells express the senescence-associated secretory phenotype (SASP), characterized by the release of high levels of cytokines, chemokines and proteases. While this is beneficial in some roles, such as wound healing, if they are not cleared (i.e., due to immune aging), SASP components can contribute to immunosenescence and poor immune responses. “The SASP contributes to the environment in the body being very pro-inflammatory and not conducive to a good immune response,” says Bartley. “I’m currently investigating whether eliminating these senescent cells prior to vaccination can improve vaccine response by reducing that pro-inflammatory, aged environment.” Rather than directly targeting immune cells, Bartley’s research targets aging physiology as a whole. “The pillars that drive aging are things like cellular senescence, epigenetic alterations, deregulated nutrient sensing and altered intracellular communication,” she says. “My kind of research, called geroscience, looks at targeting those pillars with different interventions to try to delay aging physiology to improve immune function and overall health span.” WHAT DOES THE FUTURE OF AGING HOLD? Maintaining quality of life and independence are key concerns for healthy aging. Although there are contributing factors, such as genetics, limiting immunosenescence may be able to postpone the onset of age-related disease and improve recovery and outcomes from infectious diseases, increasing the health span of older adults. “I think we have a lot of promising interventions coming up,” says Bartley. “But, I think that the best responses are going to be combinations of different things – optimizing exercise and nutrition, then considering pharmaceutical intervention – and it’s going to take a lot of research to figure out that personalized medicine approach.” While pharmacological, specifically personalized support for immunosenescence may not be ready for clinical use just yet, all three researchers stressed that there is an easy, already available method to help delay immune aging: regular exercise!⚫ 24 iStock P radipta Ghosh M.D. is professor of medicine and cellular and molecular medicine at the University of California (UC) San Diego. She is also the founding director of the Institute for Network Medicine, which is home to four centers of transdisciplinary science. To say Ghosh has a “full” career would be an understatement. But if that’s not enough, she’s first and foremost a physician–scientist and an elected member of the American Society for Clinical Investigation and the Association for American Physicians, two milestone achievements for anybody on this career path. This makes her one of a special breed of individuals driven to make a difference not only directly to patients, but in the pursuit of research that goes deep into understanding, treating and preventing the conditions that ail them. Ghosh's vision is to enhance, enrich and improve human existence by using the fundamentals of the “intranet of cells” paradigm to drive disruptive research in biology, medicine and engineering. In an exclusive interview with Technology Networks, she offers her guidance on becoming a physician–scientist for those who are or are considering following in her footsteps. Karen Steward: What advice would you give to anyone considering a career as a physician–scientist? Pradipta Ghosh: My first piece of advice would be: don’t go into it; that is unless you absolutely want to do it for the right reasons. Let me explain. It takes courage, sacrifice and a certain degree of altruism to get into either of these careers (i.e., physician or scientist). But to want to do both, one needs to be foolish and hungry. I highly recommend that everybody considering this career — at various stages of their career — monitor their commitment by taking the “mirror challenge” that Steve Jobs cited, among the many pearls he shared in his 2005 commencement address at Stanford University. Jobs narrated that, at the age of 17, he came across a quote that went something like: “If you live each day as if it was your last, someday you’ll most certainly be right.” That quote had a long-lasting impression on him and since then he looked in the mirror every morning and asked himself: “If today were the last day of my life, would I want to do what I am about to do today?” He went on to say: “And whenever the answer has been 'no' for too many days in a row, I know I need to change something.” I did not read/hear this commencement address until much later; but when I read it, I realized that I had set up a similar dial of commitment internally. I kept asking myself, repeatedly at every turn of my career, if I was enjoying this for the right reasons, to justify leaving my birthland, deserting my family and putting them through immeasurable grief, denying my son access to his grandparents' love and robbing my country of a doctor it produced. I always put the price on one pan of the weighing scale and my dreams/results in another. I was relieved to hear a voice say: “yes.” Nowadays I just use the mirror test, and so far, the answers have been: “hell yes!” Chasing Dreams, Overcoming Obstacles and Making a Difference in the World of Medicine and Science KAREN STEWARD, PhD 25 Dr. Pradipta Ghosh My second piece of advice would be: marry right; pick a good corner (wo) man. Your family needs to be ok with not just accepting you for being foolish, they must be cheerleading you on many days, and give you first-aid on other instances when you are all bruised/scorched up after a rejection of some kind. But most importantly, make sure that they want this as much as you want it. There is a Japanese proverb that says: fall seven, rise eight. I have my own version of it: fall seven, rise eight and recruit a “corner (wo) man.” In the world of boxing, a corner man is a person who is permitted to be present in a fighter's corner during a boxing match to provide advice or assistance to the injured. I lucked out that my spouse not only understood "why" I chose this career path but told me that he was proud of my choice. I liken such support to a building's foundation: unseen but essential. My third piece of advice would be: find mentors who have time for you. The best mentors are those who are able (pioneers and successful), available (access to their time, attention and office) and who know how to enable. Both my mentors – Kornfeld and Farquhar – were able. One is the father of glycobiology and another the mother of modern cell biology as we know it! Both were available because they hardly traveled (almost never). I had unbridled access to their time, interest, hearts, minds, networks and offices. Both had an open door/no appointment policy, which allowed me to watch their styles, approach to anything (conflicts, etc.), disciplined and principled behavior traits that were the basis for the longevity of their own careers and, most importantly, learn what it takes to build a legacy/ field/paradigm. Both were enablers: their roles changed, sometimes multiple times a day: therapist; guide; advisor; cheerleader; confidant; parent; coach; friend and colleague. And yet it remained constant – they were mirrors – just reflected the cold, hard, naked truth and, most importantly, what I could grow up to be if I worked on my deficiencies. I say this often to those early in their career that I had no easy way to produce an excuse for my failure because of who mentored me. I always say that my time with Kornfeld made me fall in love with this career, and my time with Farquhar ensured that I gained the skills to sustain and thrive in it. From Farquhar, who is remembered for her contributions over seven decades as a pioneering microscopist, an inspiring researcher, mentor and eminent leader of cell biology, I learned countless invaluable lessons. The time she invested in me equipped me with everything she deemed essential for my growth. She introduced me to her first postdoctoral fellow, Dorothy (Dee) Ford Bainton, M.D (a physician–scientist, a hematopathologist and the former vice chancellor of academic affairs at the University of California, San Francisco), subtly planning the final chapter of her legacy and leaving nothing to chance. Shortly after her passing in 2019, Dee and I co-authored the “In Memoriam” article for the National Academy of Sciences, in which we shared how forIf people are right in saying that love and romance are illogical, then being a physician–scientist is less of science, and more of romance and passion. You've got to love it, all parts of it. 26 iStock tunate we feel “to have been fellows in her laboratory, experiencing her humanity, generosity, high ethical standards and unwavering commitment to excellence”. Her influence has been profound, and I am deeply grateful for the foundation she provided, which continues to inspire and guide me. My fourth piece of advice: timing is key when deciding to go together or go solo. When faced with the choice between working alone or collaborating, consider going solo initially (early career), but opt for collaboration later (mid–late career). Why? Because if you're aiming to pioneer something groundbreaking, whether it's a new paradigm or an entirely novel field, you'll need others to share your vision. My final piece of advice: immunize yourself against paralyzed academic investigator's disease syndrome (PAIDS). In a 1986 JCI piece, Joe Goldstein reminds us of the dangers of fixating on superficial concerns rather than delving into the deep mechanisms of disease. By focusing on uncovering the fundamental workings of guanine nucleotide exchange modulators, I embarked on a journey that led me from the micro level of amino acids to the grand scale of human biology. This level of breadth and depth ensured that we would never really run out of ideas (i.e., we derisked) and that we could drive progress and innovation in whichever area of medicine our work would take us. In conclusion, I hope that I have not discouraged anybody or intimidated them. My journey highlights the endless possibilities that this career has to offer. Every step, from my decision to come to the States to my deliberate choices in seeking mentorship and making bold decisions on the kind of science and collaborations to pursue, has shaped my journey. Finally, I would be remiss if I did not add something important, and this is about UC San Diego, which holds a special place in my heart. Despite tempting offers elsewhere, repeatedly, I stayed because of its unique environment that encourages innovation and fosters a culture of support. Still a young institution, it has the start-up mentality where hustling and getting things done is encouraged. If you have a vision, you are free to chase it. The collaborative atmosphere and the culture of a relatively flat organizational structure at UC San Diego create what we, in medicine, refer to as the Swiss cheese model. This model offers a valuable perspective on managing errors within complex organizations. Imagine the organization as a stack of cheese slices, each representing a layer of support. Even if leadership changes or administrative colleagues leave their positions, or if not everyone in a position of power supports your ideas, it's rare for all the “holes” to align. This ensures that good ideas are less likely to fall through the cracks. As I reflect on my journey, I am grateful to have had the right preparation, the right mentors and the right environment. As a proud product of the UC San Diego Physician–Scientist Training Pathway, I am excited for the journey ahead, knowing that every challenge is an opportunity to learn and grow. Here's to chasing dreams, overcoming obstacles and making a difference in the world of medicine and science. ⚫ If you're committed to winning over skeptics, it's crucial to understand their perspective and provide the evidence they need. If obtaining evidence requires expertise beyond your own, strategic collaborations are key. Remember, when you go together, you can go much farther. Two key things to remember are that it’s a marathon, not sprint and that you can do everything, but just not all at once. Read Ghosh’s full interview over on the Technology Networks website. 27 iStock I t is estimated by the World Health Organization (WHO) that by the end of 2022, 39 million people were living with human immunodeficiency virus (HIV), and in that year alone, 630,000 people had died from HIV-related causes and 1.3 million people had acquired the disease. With the assistance of 11 UN cosponsors, UNAIDS is hoping to end the HIV and AIDS epidemic by 2030. This article will explore the difficulties faced in attempting to treat HIV, an innovative prevention strategy and the possibility of a cure. Unveiling the Progress and Challenges in the Fight Against HIV KATE ROBINSON HIV IS AN ONGOING PUBLIC HEALTH ISSUE, BUT PROGRESS MAY BE PUSHING US TOWARD A POTENTIAL CURE AND MORE EFFECTIVE TREATMENTS. Acquired immunodeficiency syndrome (AIDS) AIDS is a disease that occurs when the immune system is damaged by HIV. When treated, HIV is prevented from progressing, so many people with HIV do not develop AIDS. A person with HIV is considered to have AIDS either when the number of CD4 (a type of white blood cell) cells drops below 200 cells per cubic millimeter (a healthy person has anywhere from 500 to 1,600 cells per cubic millimeter) or if they develop one or more opportunistic infections. Without treatment, people with AIDS typically survive around three years. 28 iStock CHALLENGES IN HIV MANAGEMENT HIV is a retrovirus and can integrate its genetic material into host genomes, making it difficult to treat, and currently lacking a cure. If left untreated, HIV can lead to acquired immunodeficiency syndrome (AIDS). “HIV can establish latent reservoirs within our body. What this means is that they can hide within cells in our body and lay dormant for a long period of time (e.g., months or years). Once they become active, they can immediately replicate and infect other immune cells,” said Dr. Emmanuel Ho, a professor at the University of Waterloo. “HIV is able to alter its genetic makeup to avoid our immune system or develop resistance against anti-HIV drugs. HIV can also infect and kill immune cells in our body. As a result, these immune cells will no longer be able to participate in the fight against HIV.” Combined antiretroviral therapy (cART) is currently the only treatment for HIV. cART uses a mix of different antiviral drugs to stop HIV replicating. “cART targets the virus at several key stages of its infection and replication cycle. By doing so, cART reduces the amount of virus in the body to undetectable levels, thereby protecting and preserving these cells and the host's immune system,” said Dr. Jamie Mann, senior lecturer in vaccinology and immunotherapy at the University of Bristol. “When HIV infects T cells, on rare occasions, rather than the virus replicating and killing the host cell, the virus becomes dormant. In this dormant state, the virus is not susceptible to cART and can exist for a very long time.” Although cART is the main treatment for those living with HIV, this therapy cannot eradicate the latent reservoirs developed by the virus, so the treatment must be ongoing to be effective. While necessary, long-term use of cART is associated with toxicity and drug resistance. There is also a global disparity in access to treatments: • Approximately 10 million people living with HIV still do not have access to antiretroviral therapy. According to the 2023 UNAIDS report, only 43% of children living with HIV have access to life-saving medicine. • Over 25 million people living with HIV at the end of 2022 were in Africa. Gender inequalities continue to make an impact on the HIV/AIDS response, particularly in sub-Saharan Africa. In 2022, women in the region accounted for 63% of new infections. Worldwide, this figure was 46%. • Adolescent girls and young women in sub-Saharan Africa are at a higher risk of infection than other groups, in part due to violence, stigma, discrimination and harmful laws and practices. Other factors impacting the odds of infection include unstable housing, lower levels of education, poverty and food insecurity. • Across the globe, HIV prevalence was 14 times higher among transgender people, 11 times higher among men who have sex with men, 7 times higher among people who inject drugs and 4 times higher among sex workers in 2022 when compared with adults in the general population. “Stigma, discrimination, healthcare access and treatment adherence issues will all contribute to different populations facing distinct challenges when attempting to cure HIV,” said Mann. PROTECTING AGAINST SEXUAL TRANSMISSION OF HIV Dr. Emmanuel Ho leads a research group focused on developing and characterizing innovative drug delivery strategies, including nanomedicines, medical devices and biomaterials, for the treatment and prevention of HIV/AIDS, among other diseases. Ho recently developed a novel nanomedicine loaded with genetic material called small interfering RNAs (siRNAs) to fight HIV. siRNAs are non-coding double-stranded RNA molecules, typically used to silence a gene of interest. These RNA interference tools are useful in the study of gene function and can even be utilized for the treatment of diseases such as cancer. “siRNAs will play an important role in the development of novel HIV therapeutics. If we can identify a ‘target’ (e.g., gene) in our body that promotes or enhances HIV infection, as long as Even though treatment can help to effectively manage the condition, some immune cells go into a dormant state but still contain viral DNA and can reemerge once treatment ceases. 29 iStock we know the genetic sequence of the target, we can easily design siRNAs to bind and knockdown the expression of that target,” said Ho. The nanomedicine is intended to reduce the expression of CCR5 – a gene that encodes a protein expressed by T cells and macrophages, known to be an important co-receptor for HIV to enter cells – to prevent HIV from attaching to and entering host cells. “This gene plays a role in the HIV infection process. By reducing the expression of CCR5, we hope to reduce HIV infection,” explained Ho. By releasing a second siRNA to reduce the expression of Nef, a protein produced by HIV to inhibit autophagy, the nanomedicine can reactivate autophagy to eliminate the HIV still present in the cells. As Ho explained, “If, unfortunately, HIV is still able to infect immune cells within the body, we hope that our nanoparticles can reactivate autophagy.” When administered directly into the vagina, naked siRNAs have difficulties in achieving efficient mucosal uptake due to their rapid degradation. To get around these issues, Ho’s team encapsulated the siRNA in PEG-PLGA polymer nanoparticles. The nanomedicine was developed to be delivered intravaginally to protect against sexual transmission of HIV. However, intravaginal delivery can come with challenges. “In order to deliver nanoparticles to the submucosal layer where immune cells are located, it will first have to move across a layer of cervicovaginal mucus, which can trap the nanoparticles. Afterwards, it will have to penetrate across an epithelial layer. Finally, it is important to have the nanoparticles enter the appropriate cells,” explained Ho. The team plans to optimize the nanoparticle system to attempt to achieve 100% protection against infection. LOOKING AHEAD: IS A CURE ON THE HORIZON? While infection with HIV is treatable, there is no cure available. Dr. Jamie Mann is interested in addressing this issue with the development of novel therapeutic and prophylactic vaccines against HIV. “The global distribution of HIV subtypes varies, with certain subtypes being more prevalent in specific regions. This variation presents unique challenges for an HIV cure, as transmission, disease progression and responses to treatments differ. Ultimately, the cost and complexity of the treatment must be such that it is easily accessible for all who require it,” said Mann. Mann recently co-led an international study to demonstrate the ability of a new therapeutic to cure HIV. The therapeutic, an HIV-virus-like particle (HLP), can reactivate the virus when dormant, rendering it susceptible to cART and the immune system. Using blood samples from 32 participants living with chronic HIV, who were on stable cART for a median of 13 years, the team found that HLP was able to specifically target just the immune cells containing latent HIV reservoir and purge these cells of their HIV. “Our data shows that divergent strains of HIV are also susceptible to the same HLP treatment, suggesting that the HLP could have global applications as a therapy,” said Mann. HLP are engineered to resemble HIV and lack a viral genome, making them incapable of causing an infection or replicating. These particles can be administered by intramuscular injection. The study shows that the HLP reverses latency irrespective of the subtype of the individual’s infection. Mann and the team plan on transitioning this work from the lab to clinical trials. “These trials will allow us to rigorously evaluate the effectiveness of our strategy in a controlled setting and hopefully bring us another step closer to making a cure a reality.” Research is driving the development of new treatments and could introduce a cure for HIV, but ending this epidemic will be a global effort, requiring improved access to preventatives, therapeutics and education for at-risk groups. ⚫ It’s simple, just choose the groups and click the bubble. Our Facebook groups allow you to keep up to date with the latest news and research and share content with like-minded professionals. With three diverse groups there is something for everyone. Hi. How are you? Have you seen our Facebook groups? Come join the Neuroscience, News and Research Group here. Discover the Applied & Analytical Sciences Network Group here. Explore here. No I haven’t. Could you tell me more? Sounds great! How do I join? 31 iStock B ack in March 2020, Resia Pretorius was virtually alone in her lab at Stellenbosch University, South Africa. “We were in a hard lockdown. I was the only one in the lab, basically,” she recounts. A distinguished research professor specializing in blood coagulation, Pretorius was using her expertise to help understand how SARS-CoV-2 – the newly named virus that had just shut down the world – was affecting patients' blood. She began her research by adding amyloid clotting biomarkers to blood samples collected from acute COVID patients and inspected the results under a microscope. “I said, ‘OK, let’s see where I get.’ And I was knocked out of the room,” she tells Technology Networks. “I couldn't believe what I saw; these amyloid signals were everywhere. And I got back to the control sample and did the same, and I saw little bits, but not much.” Pretorius had become one of the first in the world to discover that COVID-19 could induce widespread clotting in the blood of patients. At the time, however, the finding was contrary to the growing assumption among clinicians that the viral disease thinned the blood of patients and that anticoagulants could pose additional risk to life. “Everyone was thinking, ‘Oh dear, it’s a bleeding disease,’” Pretorius recollects. “People were terrified that if you treat acute COVID with anticoagulants you will have everyone going into bleeding and dying. At that stage, nobody understood the disease – that it was an endothelial vascular disease. Everyone was saying it’s a lung disease, and they were all wrong.” Fortunately, for a few acute COVID patients in Stellenbosch, one doctor, a colleague of Pretorius’s, was convinced enough by her findings to administer blood thinners. “He lost six or seven very ill patients; the rest all recovered,” she says. “Now, you must remember at that stage, he was in a very, very precarious position. He knew he was helping his patients, but everyone around him said you are going to kill them. But his patients recovered really well.” Not only did most of the patients go on to recover from SARS-CoV-2, but they were also seemingly spared from any lingering or new symptoms post-infecHow Long COVID Research Could Change the Way We Think About Blood Microclots LEO BEAR-MCGUINNESS KNOWLEDGE OF THE CONDITION’S MICROCLOTS COULD MAKE A MACRO DIFFERENCE 32 iStock tion – a phenomenon that would come to be dubbed “long COVID”. This particular fortune began to deeply intrigue Pretorius as anecdotes and research papers detailing a global long COVID crisis mounted. Were anticoagulants the answer to this new chronic malady? To find out, she would first have to sample blood from long COVID patients. CLOTTED TEAM “I then got hold of some patients who had been in hospital on respiratory,” says Pretorius. “They had recovered, but they weren't the same. So, I got the first South African long COVID patients by searching around for people and saying, ‘Are you okay? Are you recovered?’ And they said they're not; they’ve got this brain fog; they suddenly can’t count – typically what you find in long COVID. So I got the first few patients’ blood samples.” And what did she find? The exact same clotting pattern observed in the blood of acute COVID patients. “We did our first trypsin digestion step, which is a bog-standard method for mass spectrometry, and we looked at the sample and it was like a ray of light coming through the lab,” she says. “We looked at the controls, the diabetes [blood taken from diabetes patients], the acute, the long COVID. I could see nothing in controls, in the diabetes, because all of the plasma was perfectly digested, as you would expect, but I could see all the clots still in the acute COVID and long COVID.” This observation seemingly confirmed a biomolecular link between the immediate symptoms experienced by acute COVID patients and the lingering symptoms of those with long COVID. But a key question remained: what had prevented the trypsin from performing its usual thinning effect? “We went back to the drawing board,” she recounts, “and we said, ‘OK, so, trypsin, which is an enzyme that digests protein, that doesn't seemingly work for acute COVID or long COVID.’ So we developed a second trypsin digestive process. And when we ran proteomics [experiments], we found all the proteins that you would expect – the fibrinogens, the alpha and the beta, all of those – and we found another molecule: alpha 2-antiplasmin, and that molecule prevents clot breakdown.” “So now we had an answer as to why trypsin doesn’t break down the clots,” she says. Armed with this new understanding, Pretorius and her team at Stellenbosch felt ready to share their discovery to the global research community. They soon filed a patent for their clot test and drafted a paper on their work. Just before sending the manuscript off for publication, however, a colleague of Pretorius’ made one small suggestion. “She said, ‘This is really nice. However, dense amyloid deposits is too difficult on the ear; change it.’ And I was sitting there thinking, ‘What else can I call it?’ And ‘microclots’ just came to me,” says Pretorius. “And 10 minutes before I submitted the paper, I changed the words to microclots, and that’s where microclots started.” It proved to be a canny move in medical marketing. Soon the word “microclots” began clogging up long COVID online support groups. Pleas and questions swirled across social media. Did every long-hauler have clots thickening their blood? Could the clots explain every symptom or just the crushing fatigue that characterized most long COVID cases? And, 33 crucially, could blood thinners help rid sufferers of the minuscule globs? As a blood coagulation researcher rather than a clinician, Pretorius wasn’t able to fully answer the last question, which has been posed to her many, many times since her microclot paper was first published. She could not conduct any clinical trials that may prove the benefits of anticoagulants – although she does believe the drugs, in some quantity, could help some patients. In lieu of such trials, though, some desperate long COVID patients have sought to thin their blood by other means. INFLAMED IN THE DEEP VEIN Since Pretorius first published her findings, many sufferers have trialed nattokinase in the hopes of bursting their microclots and reducing their debilitating symptoms. Some researchers and clinicians have cast doubt, however, on whether the protein, when taken as an oral supplement, still exhibits any clot-busting effects once digested in the gut. Other researchers, though – including Pretorius – have upheld its medical potential. “Nattokinase, instead of blocking the clots, breaks down the clots,” says Pretorious. “So it’s a safer option than triple anticoagulation therapy, because triple anticoagulation therapy blocks the platelets to hyper-activate and it prevents new clots to form. But there’s a risk; you could bleed. Nattokinase breaks the clot down and you don’t have the worry that you’re going to bleed. It acts on the clot that’s already there.” Given the relative safety of nattokinase when compared to blood thinners like warfarin or clopidogrel, Pretorius doesn’t see the harm in long COVID sufferers trying out a course of the health supplement. If taken in safe but high enough doses, it may just help give the body’s damaged endothelial layer time to heal itself, if only slightly. “The clotting issues started in a perfectly healthy individual with acute COVID,” Pretorius explains. “Something triggered then a continuation of clotting pathology that never was taken care of. The bottom line is, if the clotting pathology was taken care of in the acute phase, nobody [would have] went into long COVID. But the clotting pathology just continued and made massive damage to the endothelial layers.” If all of your endothelial layers are damaged, oxygen transport can’t go to your muscle,” Pretorius explains. “Your body will have this persistent post-exertional malaise. [As for] brain fog, your blood– brain barrier is vasculature.” “We think long COVID symptoms [are due to] a damaged endothelial layer,” she continues. “Do we say microclots cause it? No. We say the spike protein [of the SARS-CoV-2 virus] and inflammatory molecules, antibodies, auto-antibodies – all those things cause it, but [microclots] are central in the disease pathway.” “Now, what do you do?” she asks. “There’s no real treatment for endothelial damage. So we thought if we could get rid of the clots and you get rid of the platelet hyperactivation, then you get to give your endothelial layers a chance to heal. If that happens, you’ve got a fighting chance that the person with long COVID might be better.” MORE TESTING, MORE BLOOD CLOTTING CONDITIONS While countless long COVID sufferers put Pretorius’s theory to the test, her new focus is raising its awareness. Not only could wider recognition benefit long COVID patients across the globe, but also thousands of patients with other inflammatory illnesses. “Rheumatoid arthritis, psoriasis, Parkinson’s, Alzheimer’s – in all of those “The issue is, what are the dosages?” she asks. “Can triple anticoagulation work for 5% of the people? 10%? 50%? 80%? We don’t know that until we do a proper clinical trial.” Nattokinase is an enzyme isolated from natto, a traditional Japanese dish made from fermented soybeans. It exhibits strong fibrinolytic activity when in contact with human blood clots. Endothelial cells form a single cell layer that lines all blood vessels and regulates exchanges between the bloodstream and the surrounding tissues. 34 iStock diseases, you will have inflammatory molecules in circulation,” says Pretorius. “They [the inflammatory molecules] will bind to the endothelial layers via receptors, then we’ll have a protein–protein interaction to change the intimate amyloid shape.” Sepsis, in particular, has already been shown to have the exact kind of microclots that can be detected by the test, as evidenced by the recent research of Cheng-Hock Toh, a professor of clinical infection at the University of Liverpool. “Professor Toh’s group did our method,” says Pretorius. “And they found that by detecting microclots in the sepsis patients, they could predict who [would have] died and who would not. The microclot load during the sepsis event, if that was high, then it predicted whether you recover or not. And they suggested that this is a first for an ICU condition to use as a possible predictor of how sick the individual is.” “Hopefully, research like that will point to uses of looking at it as a diagnostic tool to prevent disease progression – in the case of sepsis, perhaps even suggest how sick the patient is. I hope this could be a diagnostic that they could just add on – an add-on biomarker as part of a broad spectrum that you are looking at. Look at the D-dimer, look at platelet markers, look at antibodies, auto-antibodies, but just have this as an add-on to further direct clinician approaches to treatment.” “Fifteen years from now, I hope that this method will be in every single pathology lab,” Pretorius enthuses, “that anyone with long COVID or any inflammatory disease that might think that have gotten a clotted pathology, can go to a laboratory and ask for the test and get results from it.” ⚫ “Microclots are not only found in acute COVID and long COVID, they’re also found in all of the others,” she says. 35 iStock F or most scientists, publishing their findings in peer-reviewed journals is a necessity. There are many motivators that drive them to do this, from satisfying funding conditions, meeting the goals of their employers and opening up future funding opportunities, to advancing their own careers. But ultimately, without the sharing of findings with peers, scientific advancement is held back. However, the choice of where to publish can be bewildering and the process time-consuming and lengthy. What should scientists consider — impact factor, commercial vs society publishers, review process, ease of submission — the list goes on. And what drives those publishers — profit, scientific integrity, community, shareholders…? In a bid to serve the scientific community as best they can, a coalition — Purpose-Led PublishingTM — has been formed between three publishers in the field of physical sciences: the American Physical Society (APS), IOP Publishing and AIP Publishing. We spoke to Rachel Burley, chief publications officer at the APS, to find out what Purpose-Led Publishing is and how this initiative could benefit the scientific community. Karen Steward (KS): Could you tell us what the concept of “Purpose-Led Publishing” is and how it is different to other coalitions that we see between publishers? Rachel Burley (RB): Purpose-Led Publishing is a coalition of three publishers in the field of physical sciences: AIP Publishing, the American Physical Society and IOP Publishing. Our organizations are non-profits with primary missions to advance physics, disseminate knowledge and support the physical sciences community. Together, we have defined a set of industry standards that underpin high-quality, Scientific Publishing Coalition Sees Purpose Lead the Way KAREN STEWARD, PhD 36 ethical scholarly communications and that we commit to adhere to through our coalition’s promise. While there are other groups of academic publishers that meet regularly to share knowledge, information or best practices, our coalition is discipline-specific and community-oriented through our scholarly societies. We maintain close relationships with our communities across a range of activities in addition to our journals, providing additional services like annual meetings, special programs, awards and professional development resources. KS: How did the coalition between AIP Publishing, the APS and IOP Publishing come about? RB: Our organizations have been interconnected in different ways over many years. We regularly meet at industry events and through various publishing groups. Recently, our discussions have focused on how we can better convey the value we provide to the physical sciences and related communities. In a world where academic publishing is often seen as primarily profit-driven, it can be challenging for our small organizations to communicate that our impact on our communities takes precedence over profitability. Together, our publishing portfolios represent a significant share of the high-quality journals in the physical sciences and related fields. Through the Purpose-Led Publishing coalition, we can pool our resources and collaborate to amplify our message and reach a broader audience. Our discussions revealed a strong alignment in our commitment to ethical publishing practices, reinforcing our collective promise to prioritize purpose over profit. As our teams worked together over the following months, there was a growing sense of excitement about the ways in which the coalition could evolve, aiming to co-create new tools, resources or initiatives enhanced by collective effort. Building on that momentum, three months after the launch of the Purpose-Led Publishing coalition, we have several projects well underway that we will be excited to share over the coming year. KS: What were the motivators for working together rather than competing with each other? RB: Scholarly publishers have been competing for a long time, but we believe this is self-limiting. We can offer more through collaboration, which increases our value to researchers. No two journals are identical in aims and scope, level of selectivity or readership, making our combined portfolio highly diverse and complementary. Different journals foster distinct academic communities, enhancing engagement and collaboration within and across disciplines. Our motivation to create the coalition centers around the desire to serve our scientific community better by working together more closely to address common challenges. The benefits of working together through the promises we make to positively shift our communities’ perceptions of us as academic publishers will far offset any risk presented by competition. KS: What does this mean for scientists looking to publish their work? RB: With the academic landscape becoming increasingly complex, researchers are finding they have more and more options and decisions to make when it comes to choosing where to publish their work. Factors like a journal's scope, audience, reputation and peer review process play a significant role in decision-making, alongside the increasing pressure to adhere to open access mandates. More often than not, however, the publisher of the journal, and what they do with the money made from publishing activities do not form part of the decision-making process. With science as our only shareholder, researchers publishing with a Purpose-Led Publishing member are assured that their research will not only advance knowledge through high-quality, peer-reviewed journals but also contribute to the physical sciences community they are a part of. KS: Did you come up against any challenges during this process? How have these been overcome? RB: Our current focus is on getting a program of activities up and running. We’ve set up regular meetings and working groups to develop initiatives that will make the most difference. We are exploring how artificial intelligence (AI) can improve our services, expanding our collaborative funder engagement and looking at how we can break down barriers for more researchers to take part in the global research endeavor. It’s still early days, but it’s been inspiring to stand together to drive innovation that will create lasting positive change in our industry and throughout the scientific community. KS: What are your hopes for the future regarding the coalition and the wider concept of Purpose-Led Publishing? RB: Our hope is that the coalition will lead to more appreciation for the work that society or not-for-profit publishers do. By developing initiatives that support the physical sciences and adjacent communities, we’re demonstrating the value that our mission-driven organizations provide. And with the Purpose-Led Publishing promise, we’re building additional trust with researchers who publish in or read our journals. Ultimately, it’s about explaining that scientific publishing should exist purely for scientific and public good. We are keeping the coalition to our three organizations for the first year. Once we’re established and have a few of our shared initiatives launched, we are open to considering expanding the coalition to other like-minded, academic publishers. ⚫ Helena Slaets, Dr. Pradipta Ghosh 37 Meet the interviewees whose insights featured in issue 37 of The Scientific Observer: Dr. Emmanuel Ho is a professor at the University of Waterloo. His research group is interested in the development and characterization of innovative drug delivery strategies including nanomedicines, medical devices and biomaterials for the treatment and prevention of HIV/AIDS, cancer and chronic wound healing. Dr. Helena Slaets is an assistant professor at BIOMED, Hasselt University, Belgium, specializing in immune aging and cellular senescence. During her PhD, she studied neuropoietic cytokines in multiple sclerosis. She did a postdoc at the HeinrichHeine University, Germany. At Jessa clinical laboratory, she validated diagnostic tests for autoimmune diseases. She managed an Interreg EMR project on immune aging, leading to a European patent, and initiated research on exercise interventions' impact on immunosenescence. She also founded the Healthy Aging Research Consortium to unify aging research and facilities at Health Campus Diepenbeek and teaches Immunology at Hasselt University. Dr. Erin Allmann Updyke MD is a co-host of This Podcast Will Kill You. She is an epidemiologist and disease ecologist currently in a medical residency program to complete her training. Dr. Erin Welsh is a co-host of This Podcast Will Kill You. Welsh is a disease ecologist and epidemiologist, now working fulltime as a science communicator. Dr. Lawrence Young is a virologist and emeritus professor of Molecular Oncology at the University of Warwick’s Medical School. He is internationally known for his work on the role of virus infection in the development of cancer. Dr. Pradipta Ghosh obtained her medical degree from Christian Medical College, Vellore, in India before starting her career in science under the mentorship of Professor Stuart Kornfeld at Washington University in St. Louis, Missouri. She then moved onto an internship and residency in internal medicine and postdoctoral training in the laboratory of Professor Marilyn G. Farquhar, PhD at UC San Diego. Her postdoctoral work directly led to the characterization of a novel stratum in signal transduction by a unique class of molecules, which she christened guanine nucleotide exchange modulators (GEMs). Professor Ghosh now investigates how GEMs facilitate cellular communication, and how that influences health and disease. To enable the study of complex eukaryotic systems and to determine the foundational rules that support their communication, she founded the Institute for Network Medicine at the UC San Diego School of Medicine. This institute and its four vibrant centers unite mathematics, computer science, systems biology and tissue engineering to explore and develop new interdisciplinary tools for precision disease modeling. The institute also provides opportunities for cross-disciplinary training for graduate students and postdoctoral trainees, creating fertile ground for scientists to inspire and be inspired. Meet the Interviewees Jamie Mann, Janine Gelineau (Medical Photographer/ Multimedia Specialist, UConn Health), Niharika Duggal 38 MEET THE INTERVIEWEES Dr. Jamie Mann is a senior lecturer in vaccinology and immunotherapy at the University of Bristol. His research centers around the development of novel therapeutic and prophylactic vaccines against mucosal pathogens such as HIV and Influenza. Dr. Jenna Bartley received her BS, MS and PhD in Kinesiology from the University of Connecticut. Her graduate research focused on interrelated aspects of human health, metabolism and muscle function focusing on human subject research. She completed a postdoctoral fellowship focused on immunology and aging utilizing murine models of aging and infection. She became an Assistant Professor in 2019 in the Dept of Immunology and Center on Aging at UConn Health. Her independent research focuses on combining her unique education and training background in both murine and human subject research to focus on translational aging research. Her multidisciplinary research uses geroscience approaches to bridge the bench and the bedside to uncover common pathways among the aging process and to develop potential interventions to prevent age-related declines in immune responses, physical function, and overall healthspan. Rachel Burley has been a leader in the research communications and open science space for more than 20 years. She is currently the chief publications officer for the American Physical Society. Her background in business development and publishing has pushed leading-edge trends in scientific, technical and medical publishing. Dr. Resia Pretorius is a distinguished research professor and head of the Physiological Sciences Department at Stellenbosch University, South Africa. Her research primarily focuses on blood coagulation and circulating inflammatory markers and how these play a role in inflammatory conditions like type 2 diabetes, rheumatoid arthritis and neuroinflammatory conditions like Parkinson's disease and Alzheimer's disease. She is also director of the medical technology company BioCODE Technologies, which commercializes inflammation-centered medical technologies. Dr. Niharika Duggal is an assistant professor at the Institute of Inflammation and Ageing at the University of Birmingham with a long-standing interest in the field of immunesenescence and its impact on ageing and health. Her research interests centre around on investigating the role of microbiome changes in driving immunesenescence and is passionate about the translation of her research to pilot clinical trials investigating the potential of microbiome-based strategies in improving the health of the expanding ageing population alongside the identification of new avenues of ‘healthspan extending’ intervention strategies with industrial collaborators. She is a trustee for the British Society of Research on Ageing the oldest ageing society globally that is focusing on promoting healthy ageing. Dr Duggal is a co-lead for the BBSRCMRC funded "Food4Years" Ageing Network working towards finding critical issues within the UK food system that affect older adults. ke System Cicadas Could Help Us Develop Future Self-Cleaning Everyday Surfaces CHEDELIC CHEDELIC ISSUE 29, AUGUST 2023 WER OF PLACEBO IN WER OF PLACEBO IN The Power and Potential of Epigenetic Aging Clocks Could Psychedelics Change How We Treat Migraine and Cluster Headache? ISSUE 27, JUNE 2023 PRECISION MICROBIOME EDITING To Tackle Methane Emissions The Future of Food: Five Key Considerations in Alternative Protein Food Production The Ultimate Guide to Avoiding Predatory Conferences ISSUE 30, SEPTEMBER 2023 Exploring the Next Frontier in Food Sponsored by ISSUE 26, MAY 2023 ODEGENERATIONISSUE 28 Half-Synthetic Yeast Engineered for the First Time How Body-on-a-Chip Is Transforming Research ISSUE 32, NOVEMBER 2023 Biology NATURE'S TOOLS, REDESIGNED How Do You Make a Water Purifier From Fruit Waste? Building an Atlas of the Brain ISSUE 24, MARCH 2023 ISSUE 31, OCTOBER 2023 Little Things AN INSPIRED SCIENTIST'S PURSUIT FOR A CANCThe How Collaboration and Curiosity Make for a Successful Scientist Towards the Lab of the Future ISSUE 25, APRIL 2023 ISSUE 35, APRIL 2024 Make sure you never miss an issue of The Scientific Observer. Subscribe Now Make sure you never miss an issue of The Scientific Observer. Subscribe Now