From the Lab to the Limelight - Blog version of our #TraineeTuesday social media series
This #TraineeTuesday, we are highlighting Chase Amos, a graduate student in the De Camilli Lab! He recently published a report in Contact on the connection between the two proteins VPS13A and XK in red blood cell precursors, and a paper in Molecular Biology of the Cell.
Chase’s project in the De Camilli Lab investigates the mutation of the lipid transfer protein VPS13A, which leads to chorea acanthocytosis, a Huntington’s disease-like neurodegenerative disorder accompanied by abnormal red blood cells. The study uncovered the localization of VPS13A in a line of red blood cell precursors during their development. Additionally, the study showed that this localization depends on VPS13A interacting with a plasma membrane protein called XK. Chase and his collaborators overall found that VPS13A connects the endoplasmic reticulum (ER, a part of the cell where lipids are made) to the plasma membrane after the precursor cell matures to the red blood cell lineage, potentially forming a route in which the plasma membrane’s lipid composition can be altered directly by the ER.
[This project] answers when and where the lipid transfer protein VPS13A binds within a certain cell state (differentiation), and opens future questions on how this regulation occurs. Elucidating how the cell regulates VPS13 proteins builds the foundation to ask how this regulation may go awry during disease.
Chase Amos
Chase remains grateful to have found his interest in research early on. As a high school student, he received mentorship from a lab in the nearby medical school, Virginia Tech Carilion. There, he conducted research on how the loss of a signal that helps create connections between nerve cells (synaptogenic cue) affects the formation of tiny transport containers (vesicular trafficking) in the mouse brain, influencing communication between nerve cells and leading to subsequent changes in behavior. This experience made him “fascinated by traffic within the cell.”
He then continued his undergraduate studies at the University of Virginia. His work at UVA investigated the impact of lipid composition changes on the fusion of insulin granules. The culmination of his undergraduate work was recently published in the journal Molecular Biology of the Cell. His research revealed a correlation between the types of lipids (fatty acyl chains) in the plasma membranes of cells and how much transport carriers of insulin (insulin granules) fuse with the membrane to release insulin into the extracellular space. More disordered (unsaturated) lipids increased fusion, while ordered (saturated) fats decreased it. The study also showed that the order of the membrane, a crucial factor in fusion, was influenced by the calcium-triggered action of Synaptotagmin — a protein that controls the release of neurotransmitters at synapses and hormones such as insulin. In sum, the research indicated that controlling fats in the membrane is crucial for triggering the process of insulin granule fusion with the plasma membrane.
The ability to explain complex cell biology with biochemical mechanisms really captured me,” Chase said. “It has been a recurring interest to work at the interface of cell biology — which provides the physiology — and the biochemistry — which provides the mechanism and clockwork.
Chase Amos
With the hopes of carrying this previous work on the impact of lipids on the cell in his graduate studies, Chase was drawn to Pietro De Camilli’s work on the homeostatic mechanisms the cell uses to maintain lipid composition, as well as Yale’s expertise in membrane biology.
At Yale, Chase enjoys being a part of a vibrant circle where it is possible to learn from the work of others, in his lab and beyond. Working in the De Camilli Lab also allowed him to find a broader appreciation of cell biology, researching topics ranging from the development of red blood cells to Golgi apparatus.
After graduate school, Chase aims for an academic career in biochemistry/biophysics, focusing on the mechanisms of cell biology and guiding students who share the same goal.
Chase is most excited by contributing basic knowledge to biology. “I particularly enjoy dissecting the molecular mechanism within cells: to couple the logic of biochemistry to the physiology of cell biology,” Chase said. “This is both fundamentally important and, translationally, informs molecular targets in disease.”