MANCIA, FILIPPO, Ph.D. Assistant Professor of Physiology & Cellular Biophysics Structural biology of integral membrane proteins Office: Russ Berrie Pavilion| 5th floor | Room 528 Telephone: 212.851.5367 Fax: 212.851.5346 Email:fm123@columbia.edu

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 invaluable insight into the function of a given protein, and provide the framework to test structure-based mechanistic hypotheses. We primarily use X-ray diffraction of protein crystals to obtain structural information to atomic detail, while we employ multiple biophysical and biochemical techniques, as well as cell-based assays, for functional studies. Our efforts are currently devoted to three main areas of research:

1. G-protein coupled receptors (GPCRs): GPCRs represent the largest family of genes in the human genome. Ligand-binding to a GPCR leads to the initiation of an intracellular signaling cascade through G-protein activation. The mechanism of activation, likely shared by all GPCRs remains elusive to date. We are investigating the function of GPCRs, with a particular focus on serotonin receptors, by means of functional and structural studies.

2. Intramembrane Proteases (IMPs): polypeptide chains are cleaved within the membrane in a wide variety of regulatory cellular processes. The aspartyl-IMPs presenilins are the catalytic core of g-secretase, an enzyme thought to be involved in the onset of Alzheimer’s disease. We are studying prokaryotic homologs of presenilins and related IMPs.

3. Structural Genomics of Membrane Proteins: we interact closely with the New York Consortium of Membrane Protein Structure (NYCOMPS) center, and have contributed to implementing a high-throughput platform for expression screening and purification of membrane proteins.

Selected Publications

Mancia, F., Assur, Z., Herman, A.G., Siegel, R. and Hendrickson, W.A. (2008). Asymmetry and Ligand Sensitivity in Dimeric Associations of the Serotonin 5HT2c Receptor. EMBO Rep. 9, 363-9.

Mancia, F and Hendrickson, W.A. (2007). Expression of recombinant G-protein coupled receptors for structural biology. Mol Biosyst. 3, 723-34.

Assur, Z., Schieren, I., Hendrickson, W.A. and Mancia, F. (2007). Two-color selection for amplified co-production of proteins in mammalian cells. Protein Expression and Purification, 55, 319-24.

Mancia, F., Brenner-Morton, S., Siegel, R., Assur, Z., Sun, Y., Schieren, I., Mendelsohn, M., Axel, R. and Hendrickson, W.A. (2007). Production and characterization of monoclonal antibodies sensitive to conformation in the 5HT2c serotonin receptor. Proc Natl Acad Sci U S A.104, 4303-4308.

Mancia, F., Patel, S.D., Rajala, M.W., Scherer, P.E., Nemes, A., Schieren, I., Hendrickson, W.A., and Shapiro, L. (2004). Optimization of protein production in mammalian cells with a coexpressed fluorescent marker. Structure 12, 1355-1360.