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Michigan Postdoctoral Pioneer Program, 2020

Collaborative PIs

Mentor

Melanie Ohi, Ph.D.

Associate Professor
Research Associate Professor, Life Sciences Institute
Research Focus: Single particle electron microscopy, cryo-electron microscopy, spliceosome, pre-mRNA splicing, S. pombe, structure biology, yeast genetics, bacterial pathogenesis, membrane proteins
Website:
https://www.lsi.umich.edu/science/our-labs/melanie-ohi-lab
Email:
mohi@umich.edu

Co-Mentor

Carole Parent, Ph.D.

Lynne & Raymond W. Ruddon Collegiate Professor of Cancer Biology and Pharmacology
Professor, Pharmacology
Adjunct Research Professor, Life Science Institute
Website:
https://www.lsi.umich.edu/science/our-labs/carole-parent-lab
Email:
parentc@umich.edu

Abstract:

Title:

STRUCTURAL ORGANIZATION OF LTB4 SYNTHESIZING ENZYMES IN DEFINED LIPID ENVIRONMENTS

Neutrophils represent the first line of defense against infections and inflammatory insults. The ability of neutrophils to reach these sites, a key feature in the resolution of infections, is mediated by their capacity to sense and migrate directionally to the core of the inflammation site. Neutrophils migrating towards shallow chemoattractant gradients amplify their recruitment range by releasing the secondary chemoattractant leukotriene B4 (LTB4). LTB4 is synthesized from arachidonic acid (AA) through the sequential action of the 5-lipoxygenase (5-LO) and its associated activating protein (FLAP). LTB4 and its synthesizing enzymes are packaged and released in multivesicular body (MVB)-derived extracellular vesicles called exosomes. Remarkably, the LTB4 synthetic machinery is located in the nuclear envelop (NE). Using cryo-electron microscopy, we wish to visualize the structural organization of 5-LO/FLAP complexes in defined lipid environments and assess if activated complexes form membrane curvatures. We hypothesize that the recruitment of FLAP in NE lipid microdomains gives rise to localized regions of high membrane anisotropy that act as seed sites for the LTB4 synthesis at the nucleus of chemotaxing neutrophils. Candidate will work in a vibrant scientific environment using a combination of live cell imaging, biochemical, and structural approaches.


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