COLUMBIA UNIVERSITY • DEPARTMENT OF
Physiology and Cellular Biophysics

CURRENT RESEARCH

 

We are interested in the structure and function of membrane proteins. Proteins that reside within the plasma membrane are responsible for how a cell detects and responds to extra-cellular stimuli, of biological, chemical and physical nature. High-resolution snapshots of such molecules offer invaluaFilippo Mancia graduated in Chemistry in Pavia (Italy), and obtained a PhD at the MRC Laboratory of Molecular Biology in Cambridge, UK. His post-doctoral work was carried out in the labs of Drs. Wayne Hendrickson and Richard Axel at Columbia University.

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He is a structural biologist with considerable experience in x-ray crystallography, and more recently in single particle cryo-electron microscopy, and in production and characterization of eukaryotic and prokaryotic membrane proteins for structural studies.

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Dr. Mancia’s main research focus is on membrane protein – lipid interactions. Within this realm, his lab has recently determined the high-resolution structure of enzymes from three families, which process lipid substrates. (1) GtrB, a polyisoprenyl phosphate glycosyltransferase attaches glucose to a lipid carrier for membrane translocation and a glycosyl donor for subsequent reactions. This reaction represents the first step in all protein glycosylation and glycosylation of the cell wall. (2) ArnT uses sugar-charged donors produced by GtrB-like enzymes, and transfers the saccharide to lipid A on the cell surface of bacteria, altering antibiotic resistance properties. (3) The Mancia lab determined the structure of a phosphatidylinositol-phosphate (PIP) synthase – an enzyme required for inositol-lipid synthesis – with a bound CDP-diacylglycerol substrate. This enzyme is a member of the CDP-alcohol phosphotransferase family (CDP-APs), which catalyze the defining step in glycerophospholipid biosynthesis across all kingdoms of life. Retinoids (Vitamin A derivatives) are also lipids, and thus in this theme fits another project of the lab, aimed at understanding how STRA6-mediated cellular uptake of retinol occurs – fits into this research theme. The Mancia lab’s experience in structural biology, in overexpression of integral membrane proteins, in functional analyses of membrane proteins and in high-throughput techniques for membrane protein purification and selection, make it a unique environment for researchers interested in studying membrane protein-lipid substrate interactions, and in developing tools to advance this rapidly evolving field.

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Dr. Mancia has also been a key member of the New York Consortium of Membrane Protein Structure (NYCOMPS), located at the New York Structural Biology Center (http://nysbc.org/) where he has played a pivotal role in the design, development, implementation and optimization of the high-throughput cloning and protein production platform for prokaryotic membrane proteins successfully functioning at the NYCOMPS center. NYCOMPS has recently transitioned to a NIH-funded biomedical technology resource center named the Center on Membrane Protein Production and Analysis (COMPPÅ, https://www.comppaa.org/; Wayne Hendrickson, PI), and he serves on the executive committee for COMPPÅ.