From School Science Club to Cell Atlasing With Dr. Sarah Teichmann

After completing her PhD at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB), Cambridge, UK, Dr. Sarah Teichmann set up a group there in 2001 and became an MRC program leader in 2006. In 2013, she moved to be the first and, to date, only joint faculty member across the EMBL-European Bioinformatics Institute and Wellcome Sanger Institute, and was appointed Head of Cellular Genetics at the Sanger Institute in 2016. She has recently started a new position as a part-time Vice President Translational Research at GSK, and is the incumbent Professor of Stem Cell Medicine at the University of Cambridge.

Sarah’s research currently focuses on single-cell analysis of human tissues, and she has made several breakthroughs in cell-atlasing. Her interest in this area and its potential led her to co-found the Human Cell Atlas (HCA) international consortium in 2016, which she also co-leads. With over 3,000 members globally, the consortium is working to map every cell type in the human body and drive advances in our understanding of health and disease.

In addition to being elected EMBO Member, Fellow of the Academy of Medical Sciences and Fellow of the Royal Society, Sarah has received several awards throughout her career, including the Lister Prize, Biochemical Society Colworth Medal, Royal Society Crick Lecture and EMBO Gold Medal. Most recently, she received the FEBS | EMBO Women in Science Award 2023, in recognition of both her scientific achievements and advocacy for making science more inclusive. She is also co-founder and chief scientific officer at a new startup company, EnsoCell Therapeutics.

In this interview, Sarah shares insights into her research interests, the goals and progress of the HCA to date, as well as her thoughts on how women can begin and build successful careers in science.

Q: How did your interest in science originate? Were there any role models that inspired your career?

A: I grew up in an environment that promoted curiosity and creativity. My dad was an electrical engineer and a tinkerer at home, and my mum had studied German literature and taught English language. I loved learning about languages (including Latin) and also about science and the natural world.

At school in Karlsruhe in Germany, it was my chemistry teacher, a Scottish man called Walter Henderson, who really got me into science. His teaching was inspiring, and he ran an after-school science club. I did a research project on the changes in metabolism of leaves across the seasons, which I really enjoyed, and it got me thinking about cells and how they work.

I also remember reading a Scientific American magazine, which we borrowed from the local US military library near where I lived in Germany. I was fascinated by a particular story: the discovery of proteins called “zinc fingers”, and how they can control genes by switching them on and off. It made me want to study life at a really small scale – the molecules that are the basis of life. And as fate would have it, the story was written by Aron Klug and Daniela Rhodes, who became my colleagues when I started as a group leader at in the Structural Studies Division at the MRC LMB about a decade later. 

Q: Could you tell us more about your current research interests? When and why did you decide to focus your research in this area?

A: Throughout my career I’ve sought to understand the global principles of biological systems, from how genetic networks evolve and protein complexes assemble, to how gene expression is regulated, cell identity is controlled and how cells assemble into the human body. Whatever I do, I always try to take a “big picture”, systems view.

Currently, my lab is focused on single-cell analysis of human tissues, developing and using experimental and computational tools, to investigate which genes are expressed in individual cells throughout an organ or tissue. Single-cell genomics – and more recently, spatial genomics technologies – provides a way of understanding the rules of cell identity in the body and reveals how cells interact to form functional tissues.

I got into single-cell genomics via our work with T cells in the adaptive immune system, which are highly plastic and heterogenous. Single-cell analysis was a game changer. Over the years, we kept our interest in the immune system but broadened out, because single-cell genomics allows for an unbiased way of interrogating all the cell types of the body.

Consequently, we have generated cell atlases of various organs in the body and through development, which all include immune cells but also some of the other amazing cell types of the body. A recent exciting example is our molecular characterization of the pacemaker cells that set the pace of the heartbeat.

Q: You are also co-founder and co-leader of the HCA international consortium. Could you tell us more about the consortium, your role and any highlights so far?

A: Aiming to map every cell type in the human body, the international HCA consortium is transforming our understanding of biology and disease, and will lead to major advances in the way illnesses are diagnosed and treated. I co-founded the HCA consortium in 2016 with my colleague Aviv Regev (who was then at the Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard).

At that time, single-cell genomics technology was still fairly new, and Aviv and I saw it had huge potential to revolutionize our understanding of how the human body works. But because the human body contains trillions of cells, we also knew that no single lab, or even country, would be able to map the whole body. We needed something analogous to the Human Genome Project, but even larger – an international consortium dedicated to body mapping.

Today, the HCA has over three thousand members, from every inhabited continent, who have analyzed tens of millions of individual cells across the human lifespan. We achieved v1.0 HCA Atlases from the lung and brain last year, and are making great progress towards our core aim of creating comprehensive reference maps of all human cells as a basis for both understanding human health and diagnosing, monitoring and treating disease.

As the co-leader of the HCA, my responsibility is to make sure this fantastic community continues to thrive and achieves the goal of creating a representative Atlas that will benefit all of humanity. I want to ensure that everyone feels their voice is heard, and that we continue to attract and support amazingly talented researchers from across the world. I am involved in discussions that plan the next steps of creating the Atlas and raising funding. Aside from that, I also lead my own wonderful research group, which contributes to creating the Atlas.

Q: Have you faced any setbacks along your path to success? What have you learned from them? What more can be done to support women to begin and build a career in science?

A: When I started my research career, I was working in a very male-dominated field. Being one of the only women was challenging at times. At the same time, I have been incredibly fortunate to have fantastic mentors and supporters throughout my career, both male and female, as well as wonderful colleagues. They form a support network that can help when times get tough and help you feel welcome in the community. Having female role models undoubtedly helped – for example, my postdoctoral supervisor Janet Thornton, a phenomenal leader in bioinformatics, and my long-term collaborator Carol Robinson, an amazing physical chemist.

I should say that the world of science has changed a lot since I started my career over twenty years ago. Diversity and inclusion are seen as important, thankfully. Anyone, regardless of gender, ethnicity, disability, etc., should feel included and welcome in the community, and we should have a scientific workforce that reflects the diversity of society.

I believe that diversity is strength – and that a diversity of perspectives, approaches and skills incubates the best science!

Q: What do you enjoy most about your work and what would you say are your proudest achievements?

A: The things that I love the most about working in science are interacting with people and discussing data, results, interpretations and ideas. When a student, postdoc or staff scientist comes into the office with an exciting new piece of data, it’s just brilliant! I’ve got an incredible team of 17 scientists and it’s hugely rewarding to supervise their work and support their careers – it’s fantastic to follow their trajectories after they leave the lab and achieve success either in academia or industry. The further you progress in your own career, the larger these networks become, and you end up with supportive friends and collaborators all over the world.

There are actually a couple of different achievements I’m proud of. Firstly, defining the stereotypical pathways of assembly and evolution of small soluble protein complexes, and then taking this understanding of how proteins interact into mapping of human cells and tissues, for example, in the maternal/fetal interface. The molecular dissection of cells and tissues in our body is an incredibly exciting journey, and the years ahead promise ever more insights with the fast-evolving multiomics and spatial technologies coming online.

Q: If you could give one piece of advice to a woman who is considering a career in science, what would you say?

A: Well first of all: 100%, go for it! As I said above, I do believe there are fewer barriers to success today based on gender, and I would encourage any young woman to consider science as a career.

In terms of advice, I think it really helps to have found a question or problem that captivates or obsesses you, even to the extent of keeping you up at night. At the same time, having allies in science and life is key, and working together with others makes the journey easier and more fun – teamwork is recognized as an important aspect of science nowadays.

There are a lot of challenges to a scientific career, regarding job security, funding, administrative burden, competition, when to start a family, etc., and you need motivation and friends and colleagues to keep you going and drive through them. Fundamentally, science is about pushing forward our understanding of how the world works, so find what dark corners of the universe you feel really drawn to light up.

Dr. Sarah Teichmann was speaking to Anna MacDonald, Senior Science Editor for Technology Networks.