First-of-Its-Kind Lipidomics Excellence Award Acknowledges Forward-thinking in a Rapidly Growing Field
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Dresden is the charming capital of the eastern German state of Saxony. Here, delicious freshly baked food is aplenty, classical music drifts out of shop windows as you saunter on by, and the cobbled streets are adorned with ornate Baroque architecture.
The city is a sweet spot for history, art and culture lovers alike. However, it's present and future position as a hub for innovative scientific research and discovery is equally as is impressive and draws in scientists from across the globe. Dresden is home to 46 research centers, including four Max-Planck Institutes, two Helmholtz Facilities and five Leibniz Institutes.
Dresden, Germany. Image credit: Molly Campbell.
Insight into the lipid cosmos
My visit to Dresden orientates around a scientific research field that has garnered increasing attention over recent years – lipidomics. Research in this field entails the characterization and functional analysis of lipids: complex hydrophobic polymer biomolecules that drive metabolic regulation at both the cellular and whole-organism level. Advances in our understanding of the integral role that lipids play in health and disease have been enabled by developments in mass spectrometry (MS)-based technology for small molecule analysis. In the heart of Dresden, Lipotype GmbH host the press talk for their Lipidomics Excellence Award (LEA), the first prize to recognize innovation and drive for novelty in researchers using lipidomics.
Featuring an impressive panel of world-renowned researchers, including Professor Kai Simons, Director Emeritus of the Max Planck Institute of Molecular Cell Biology and Genetics and CEO of Lipotype, Professor Michele Solimena, Professor of Molecular Diabetology, TU Dresden, and the LEA laureate Professor Anne Claude-Gavin, Louis-Jeantet Professor at the University of Geneva, the press talk delivered its promise of being an educational event that explored the future directions of this exciting field.
Lipotype GmbH is a Max Planck spin-off company founded by Professor Simons that offers quantitative lipidomic analysis from clinical and biological samples using novel high-throughput shotgun lipidomics technology. The Lipotype team is composed of experts in membrane and lipid biology/chemistry, MS and bioinformatics. Their experience is based on years of academic research focusing primarily on the role of lipids in various cellular processes and on methodological/ technical aspects of lipidomics.
The cell and the city
Professor Simons opens the event with an eloquent metaphor, likening the cell to a city: "Think of a city, a city that has walls surrounding it and is compartmentalized into different sections. For example, a city might have a powerplant. Similarly, the cell has mitochondria. These individual compartments in the cell are "walled" by plasma membranes composed of lipids and proteins. 30% of proteins in an organism can be found within the plasma membrane, and lipids help the proteins to serve their physiological function within the cell."
Throughout his impressive career, Simons' research has focused on cell membrane organization and function, pioneering the concept of lipid rafts. Now, his focus is on translating lipidomics and lipid analysis to clinical and industrial applications.
"Lipidomics is a niche area," he emphasizes. "But there is a growing concentration of researchers that want to know what lipids do, and we want to continue to stimulate research in this area."
Want to learn more about the basic principles of lipidomics? Check out our article, Lipidomics: A Rising Star in "OMICS" Research.
Professor Solimena is one of a growing cohort of researchers that utilize Lipotype's Shotgun Lipidomics Analysis for their research projects.
"Lipidomics is step by step revealing processes and connections that stay hidden with traditional analysis methods." He continues, "In diabetes research, we make good progress thanks to lipidomics. For example, it is now possible to define molecular lipid signatures that tell us about the development of non-diabetic to diabetes type 2 and progression towards diabetes complications."
"We want to shine a light on the fact that lipid analyses really make the difference between research and ground-breaking research: by providing new data one gains even deeper insight into the lipid cosmos. It is high time to seize the potential, let us see what there is still to discover," says Simons.
The LEA has been developed by Lipotype to encourage research in lipidomics by providing a generous research prize: 50,000 EUR worth of high throughput quantitative shotgun lipidomic analysis, in addition to a speaking slot at the EMBO workshop Lipid Function in Health and Disease that took place in Dresden over the course of last weekend.
The first prize goes to…
Professor Gavin is the first LEA laureate, awarded the prize for her research proposal in lipid-transfer proteins. Thus far, ~131 lipid-transfer proteins have been identified in humans, with varied roles such as orchestrating the transport of lipids between membranes, thereby spatially organizing lipids and connecting lipid metabolic pathways within the body.
"I spent the last thirteen years running a group at the EMBL in Heidelberg. Here we have been applying new methods to measure how lipids can interact with proteins and thereby modify the functions of the cell," says Gavin. "For this, we integrated bioinformatics, MS, metabolomic analysis and microfluidics. Since April of this year we moved to the department of Cell Physiology and Metabolism at the University of Geneva."
Professor Gavin explains the background research that has led to the development of the LEA-winning project. "We don't yet know the size of the human lipidome, but we believe there may be up to 40,000 different types of lipids in the human body. So the question is, why do we need such diversity in lipids and what do they all do? We do know from genetic studies that lipid function can be altered in metabolic syndromes, but the exact mechanism behind these alterations isn't well understood."
Lipids catch a ride
"It is important to understand that lipids inside the cell are not marginally distributed. The lipids can accumulate in different compartments inside the cell, and they can work as scaffolds for cell signalling processes or for organizing cellular function." Profesor Gavin continues, "Different organelles in the cell accumulate different lipids. We know now the steps for lipid synthesis and the enzymes that are involved, but surprisingly the enzymes can be located in different compartments inside the cell. The lipid factories are sometimes identified in distant locations from where the lipid is actually required to serve a function. As lipids are hydrophobic and cannot meet with water, they cannot freely diffuse inside the cell. For a lipid to be metabolized and have activity, they need to be transported. We still don't know exactly how this happens."
Professor Gavin will therefore use the LEA research prize to develop the first molecular cartography of the lipid "highways", providing insight into metabolic signaling pathways as well as lipid-transfer protein mediated lipid movement. This will be integrated into a molecular model to describe cell-specific cancer associated alterations. The model will help to address several medically relevant questions.
Mapping the lipidome – why now?
After the press talk concludes I interview Gavin to delve further into the specifics of her research approach. But first I want to address one particular statement from the press talk that caught my attention – the comparison of Gavin's "lipid highways" research as a "metabolomics" equivalent to the Human Genome Project that was completed 16 years ago. Why is it only now that we are recognizing the need to map lipid and protein interactions in cells at the same level of detail? Gavin tells me "It simply comes down to technology. Having the technology available is critical. If you really want to address new questions and problems in biology, you need to develop new technology. Of course, you need a biological question," she laughs, "But without the technology the research is not possible. The EMBL has been a great place for us to develop new ways to measure protein-lipid interactions in a high throughput manner, adopting microfluidic and biochemistry approaches."
Professor Anne-Claude Gavin holds the first LEA prize with Professor Kai Simons. Image credit: Lipotype.
Lipotype specializes specifically in offering quantitative lipidomic analysis, and I am keen to know how this element of the prize will help to progress Gavin's research. She explains "In biology we need to divert away from taking binary measurements and looking at whether something is simply expressed or not. It is very rare that a disease will lead to the absence of something – rather, you will have an imbalance. We need to be able to quantitatively measure the imbalance, which is why the analysis offered by Lipotype as part of the LEA is key to our project."
The high throughput analysis offered in the LEA prize will undoubtedly help facilitate the lipid highway research project. Nonetheless, I'm interested to know whether Professor Gavin expects to encounter any hurdles further downstream in the study. "One of the big challenges will be data integration, as will be producing large data sets on lipidomic and proteomic interactions. We will have to integrate knowledge on metabolism. The first challenge is to understand what we see, what is the background and what is the signal we are detecting. This is relatively basic, but it is critical so that we can derive a hypothesis," she comments. "Ultimately, we would like to be [able] to create models where we can study the physiological impact of say a gain of function in the lipid transfer mechanisms, but data integration will be a big challenge."
How much data is too much data? "To provide context, our group just finished a few screens on lipid transfer proteins that took approximately one to two years to complete, but it then took us an additional one to two years to develop the bioinformatic tools to handle the data."
Future directions in an emerging field
Lipidomics is a field that is developing fast – in 2019 it was the highest growing "omics" field, with a growth increase of 46% in publications. What does Professor Gavin think the future of lipidomics research will look like? "In the shorter term I think we really need to do our homework and understand 'what is the human lipidome?' and what function do each of these lipids serve to create a reference map," she tells me.
"In the longer term we need to understand the interactions between lipids. When you perturbate a cell there is a metabolic response and we need to chart the role of lipids in this response. It is also important that we develop a community of researchers because lipidomics is still seen as a difficult discipline."
Gavin adds, "My personal goal is to develop a technology that allows us to visualize lipids in our body and trace them as they are transported in different organs."
A lipidomics "dreamland"
To conclude, I ask Gavin how it feels to be the first winner of the LEA – albeit, her beaming expression does already provide some insight. "We are very proud. It is reassuring to see that the type of biology that we do and the technology that we have developed is useful for the scientific community, and that other people share our enthusiasm for this area of research. This [the LEA prize] is really a great opportunity and allows us to conduct measurements that would have been otherwise challenging. It is really a lipidomics dreamland," she concludes.
Whilst it seems we are still scratching the surface on the intricate nature of lipid biology, mapping the lipid highways will undoubtedly provide further insight and necessary directions for future research strategies. Congratulations, Professor Gavin!
Professor Anne-Claude Gavin was speaking with Molly Campbell, Technology Networks.