UCSD - University of California - San Diego
01/14/2025 | Press release | Distributed by Public on 01/14/2025 04:11
Itay Budin and Christopher Obara Named Allen Distinguished Investigators
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January 14, 2025Article Content
University of California San Diego Assistant Professors Itay Budin and Christopher Obara have been named Allen Distinguished Investigators by the Paul G. Allen Family Foundation. The pair will receive $1.5 million over three years to develop visualization and tracking techniques to observe key cellular functions in unprecedented detail.
The tools and techniques developed in this project will be of wide use to the cell biology community, with implications for human metabolic and neurogenerative disorders.
Budin and Obara, who holds a joint appointment in the UC San Diego School of Medicine's Department of Pharmacology, discuss their research, the importance of lipids and the role cell metabolism plays in health and disease.
(l-r): Chris Obara and Itay Budin will develop visualization and tracking techniques to observe how cells transport lipids.
What are lipids and why are they important?
Itay Budin: Lipids are fatty compounds that perform a variety of functions in our bodies. They're found in parts of our bodies that don't contain fat, like the brain, because the brain is filled with cell membranes, which are made up of lipids - and those are the lipids that my lab studies.
How will your labs work together?
Chris Obara: My background is in physics and imaging technology, and my lab develops custom microscopy and advanced imaging tools to help solve fundamental questions in biophysics, cell biology and neuroscience.
The membranes inside cells are often in these complicated shapes. A big part of my postdoctoral research was trying to understand what those shapes were and why they're important. If you want to learn more about membranes and the majority of molecules in membranes are lipids, then you want to work with a lipid expert. That's Itay.
This is an exciting opportunity for us to integrate our labs - Itay's lipid expertise along with my advanced imaging tools - to get a fuller picture of what's happening at the cellular level.
What are lipid transfer events and why do they matter?
Budin: The call for this award was on organelle communication. Organelles are structures in cells that perform jobs, just like the organs in our bodies. Our cells have many different organelles and they're predominantly surrounded by membranes, but they still need to talk to each other and they have to exchange or transfer lipids.
Lipids are transferred at membrane contact sites, which are regions in cells where organelles are just a few nanometers apart - they're practically kissing. Those are hot zones for lipid transport.
Obara: The composition of organelle membranes is a huge determinant of their function, biology, protein localization - everything. A big question in this field is understanding how membrane contact sites function. We know there are specific gene products and proteins involved. We know there are specific interfaces where they happen. But we don't have a good understanding of how the mechanism is regulated - turned on when you need it, turned off when you don't.
I think we're at a point now where, technologically, this work is feasible. Itay's lab has a family of new tools they've just developed that lets them identify the specificity of lipid trafficking between different spaces. And we have microscopy tools that can be used in complement to see these contact sites and the behavior of the lipids.
To my knowledge, no one else has the traction to go forward with this kind of research.
Budin: Being able to image lipid molecules during these transfer events is really the crux of the innovation we proposed to the Allen Institute.
What is cell homeostasis and how do lipids play a role?
Obara: One of the things that has puzzled me for many years is trying to understand how organelles synchronize biochemical reactions. Within a cell, you have all these membrane-bound compartments (organelles), but that means the molecules inside of them can't see each other. And yet they have to be exquisitely coordinated.
Definitions
Lipids: fatty, waxy or oily compounds found in the body. Lipids are an essential component of the cell membrane, providing cell protection and serving as a barrier to certain molecules.
Organelles: subcellular structures that perform specific jobs in the cell, including the nuclei, which store genetic information; mitochondria, which produce chemical energy; and ribosomes, which assemble proteins.
Metabolites: a substance made or used when the body breaks down food, chemicals or other substances. This process, called metabolism, creates energy and helps purge toxic substances.
Microscopy image showing the distribution of a common phospholipid in a human cell. Some phosopholipids have been selectively illuminated (in magenta) using genetically encoded protein sensors. These sensors will be developed to visualize lipids at contact transfer sites.
If metabolites (the byproducts of metabolic reactions in the cell) start to pile up, that's toxic for the cells and they die. So, they have to be very precise about how many metabolites are where. One of the ways that we think this is regulated is at these contact sites.
Budin: Homeostasis doesn't mean nothing is happening. As an example, if I eat a cheeseburger, I ingest a lot of lipids at once. Cells transport those lipids through an organelle called a lysosome and distribute them to where they're needed.
Later in the day, I'm not eating, so I'm not getting any dietary lipids. Now my cells need to start making their own lipids in an organelle called the endoplasmic reticulum. If I'm exercising, my cells need a lot of energy, which is produced by an organelle called the mitochondria, which is powered by lipids.
The point is that cells need to constantly change. Homeostasis at the organelle level is not static. It's actually dynamic, depending on what the cell needs to do, including, very importantly, metabolism.
It might not occur to people that a neurodegenerative disease could be linked to issues in metabolism.
Obara: It takes a lot of energy to run your brain - something like 20% of the energy you consume every day - so metabolism is very important to brain health. Because the brain is so sensitive, when something is even just a little bit wrong, it can add up over time. This is probably why neurodegenerative disorders don't manifest at birth. They manifest decades later because if the system is a little out of joint, the damage builds up slowly over time.
How do lipid transfer events impact disease?
Obara: I don't want to overstate it, but I think there is the potential to really unlock the underlying component that drives all of metabolism, which is this membrane communication within cells. As Itay said, fundamentally, metabolism is the one thing that is consistently implicated in all of these neurodegenerative disorders, the dysregulation of this process.
And it's not just neurodegeneration. There are a lot of metabolic and autoimmune disorders that we don't have a good understanding of, and one reason is because we haven't been able to visualize whole subfamilies of molecules like lipids. Now we're in this really exciting new era where those things can be directly seen and studied, and we're thrilled to be a part of it.