My lab has two main areas of interest: 1) tail-anchored (TA) protein targeting and quality control; 2) selective autophagy. Given that selective autophagy targets toxic protein aggregates and damaged organelles for destruction, these two research areas have strong conceptual ties. In many cases we are answering similar questions about substrate selectivity: What distinguishes newly-synthesized TA proteins as substrates for endoplasmic reticulum protein targeting from TA proteins targeted to mitochondria? What distinguishes TA proteins that are mistargeted to mitochondria as quality control substrates from native mitochondrial TA proteins? What distinguishes apparently damaged organelles as selective autophagy substrates from healthy organelles? To answer these questions, we are dissecting diverse molecular mechanisms that select substrates of grossly different sizes and operate on very different time scales. My lab is known for its biochemical reconstitution work in the budding yeast S. cerevisiae but more recently we have done genomics, quantitative yeast cell microscopy with theoretical modeling, and genome-wide screens in mammalian cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM127136-03
Application #
9900828
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Maas, Stefan
Project Start
2018-04-01
Project End
2023-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Weir, Nicholas R; Kamber, Roarke A; Martenson, James S et al. (2017) The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane. Elife 6:
Eapen, Vinay V; Waterman, David P; Bernard, Amélie et al. (2017) A pathway of targeted autophagy is induced by DNA damage in budding yeast. Proc Natl Acad Sci U S A 114:E1158-E1167
Zalisko, Benjamin E; Chan, Charlene; Denic, Vladimir et al. (2017) Tail-Anchored Protein Insertion by a Single Get1/2 Heterodimer. Cell Rep 20:2287-2293