CXiao-01
Structural and functional studies for a viral global SUMOylation Inhibitor Gam1
Health, human disease & diagnostics
Preferred major field of study or minimum required skills
- Major in biology, biochemistry, or chemistry will be preferred.
- Previous lab experience is highly favorable.
- Good working ethics, team work spirit and good English communication skill are required.
Scholarly significance/intellectual merit
In order to ensure their replication and survival, viruses must control host machinery. SUMOylation is a protein post-translational modification in which Small Ubiquitin like Modifier (SUMO) peptides are attached to target proteins with the purpose of altering their locations and final functions. Gam1,an early gene product of an avian adenovirus,is the first and by far the only viral protein found to globally inhibit cellular SUMOylation. However, the detailed mechanism by which Gam1 does so has yet to be elucidated. The objective of the project is to crystallize Gam1 and determine its three-dimensional atomic structure, which will shed light on the mechanism how Gam1 performs its function. The long term goal include study Gam1's interactions with its cellular target molecules. These results will deepen our understanding of Gam1's roles in viral replication and facilitate future usage of Gam1 as a cellular SUMOylation inhibitor.
Research question(s)
Structural studies of Gam1 in Dr. Xiao’s research will address the following questions:
- What do the structures of Gam1 look like?
- How does Gam1 interact with its cellular target proteins such as EloB/C and SAE1/E2?
- What is the detailed mechanism by which Gam1 globally inhibits cellular SUMOylation?
Methods/techniques/instruments to be learned/utilized
The student will engage in hands-on activities to express and purify Gam1, carry out its structural and functional studies. The student will learn molecular biological skills such as protein electrophoresis, protein expression, protein chromatography, western blot, and other biochemical experiments. The student will obtain knowledge about state-of-the-art technology such as X-ray crystallography and cryo-electron microscopy (Cryo-EM, 2017 Nobel Prize in Chemistry).