Completed Cells, Biochemistry & Physiology Genetics & Molecular Biology

Exploiting divergent biology of two fission yeasts to understand membrane function

In plain English

AI plain-English summary

Every living cell is wrapped in a greasy film of fat-like molecules called lipids, and this research will figure out exactly how the mix of those lipids controls what the film does. The problem is that while scientists know that getting the lipid recipe wrong causes disease—from diabetes to neurodegeneration—they cannot explain *how* lipid composition dictates membrane behaviour. The difficulty is that a cell's lipid mix is tangled up with its metabolism and regulation, making cause and effect impossible to tease apart. This project sidesteps that mess by comparing two species of fission yeast that naturally have very different lipid compositions but are otherwise easy to genetically manipulate. By reverse-engineering one yeast's lipid recipe into the other, the team can watch what happens to membrane properties and cellular function. This is fundamental science with no immediate practical application. The goal is to discover core principles: how the shape of lipid molecules changes membrane physics, how genetic networks evolved to keep lipid balance, and whether new lipid-making abilities drove the evolution of new cellular pathways. Past work on yeast membrane biology has revealed mechanisms of cholesterol transport and drug resistance that later informed human medicine. A deeper grasp of lipid rules could eventually help design better drug-delivery nanoparticles or understand metabolic disease origins.

View original technical description
Membrane function is fundamental to life. Deregulation of the membrane lipid repertoire has severe consequences for cellular and organismal fitness. Defining how lipid composition controls membrane organization and cellular physiology remains a major challenge in biology. Membrane lipid composition is subject to complex feedbacks and reflects the metabolic and regulatory capabilities of the specific experimental system. I propose to attack this problem by exploiting the natural divergence in membrane lipid composition between S. pombe and S. japonicus, two related genetically tractable fission yeasts with different lifestyles. I believe that our research program integrating comparative analyses and reverse engineering of cellular mechanisms with biophysics and systems approaches, provides an unmatched discovery platform capable of revealing the core principles that govern membrane organization and function. Our research will explain how changes in the architecture of glycerophospholipid fatty acyl tails affect membrane properties. It will provide insights into the organization and evolution of genetic networks regulating membrane homeostasis. Finally, it will test if acquisition of new lipid metabolic functionalities engenders diversification of cellular pathways and organismal physiology.

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Researchers

Snezhana Oliferenko (EPMC Awardee)

Related Research

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Original classification

Investigator Award in Science

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