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Research Projects

Projects for 2017 are posted below; new projects will continue to be posted through February. To learn more about the type of research conducted by undergraduates, view the 2016 Research Symposium Abstracts.

This is a list of research projects that may have opportunities for undergraduate students. Please note that it is not a complete list of every SURF project. Undergraduates will discover other projects when talking directly to Purdue faculty.

You can browse all the projects on the list, or view only projects in the following categories:

Bioscience/Biomedical

 

Structure and Function of Signaling Proteins involved in Cancer and Heart Failure

Research categories:  Bioscience/Biomedical
School/Dept.: Biological Sciences
Professor: John Tesmer
Preferred major(s): Biochemistry, Biology, or Chemistry
Desired experience:   Organic and Biochemistry lab experience preferred.
Number of positions: 2

There are two possible projects:

1) Structure and function of P-Rex1, a driver of metastasis

P-Rex1 is a guanine nucleotide exchange factor (GEF) for Rho GTPases. Rho GTPases are small G proteins which exist in inactive (GDP bound) or active (GTP bound) forms. They regulate cell migration, cell proliferation and transcription etc. Both Rho GTPases and P-Rex1 are over-expressed in different cancers and hence are important targets for chemotherapy. P-Rex1 is different from other RhoGEFs in that it is synergistically activated by the heterotrimeric G protein βγ subunits (Gβγ) and a phospholipid, PIP3. We are interested to find out how binding of Gβγ and PIP3 activate P-Rex1. Our strategy is to express and purify different P-Rex1 domains and the Rho GTPase Rac1 from E. coli and Gβγ from insect cells. We will then try to form stable complexes of Gβγ and IP4 with P-Rex1 and Rac1. This will be followed up by attempts to crystallize these complexes with the long term goal of obtaining an atomic structure.

The student will be involved in expression and purification of P-Rex1 and Rac1 proteins from E. coli. The protein purification methods involves different chromatography techniques, most common being affinity and size exclusion. This lab experience will help the student to understand how recombinant proteins are expressed and principles of protein purification and crystallization.
Overall picture of the project: The proteins purified by the student will be used for the structure determination of the complex which will give insight into how P-Rex1 is regulated.

2) Elucidation of the membrane binding mechanism of a receptor kinase

G protein-coupled receptor kinase (GRK) phosphorylates activated GPCRs on the cell surface. Different phosphorylation patterns of the receptor turn on distinct downstream pathways and lead to various functional outcomes. Therefore, GRK mediated receptor phosphorylation plays important roles in dictating the downstream pathway of receptor signaling. One critical step in the phosphorylation process is the association of GRKs with the cell membrane. Previous studies revealed that GRK5 contains specific binding sites for phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 anchors GRK5 to the membrane and facilitates its interaction with the receptor. The main goal of this project is to determine an atomic structure of GRK5 in complex with PIP2. Molecular details of how GRK5 orientates itself towards the cell membrane and how GRK5 changes its shape when in contact with PIP2 will help elucidate the molecular mechanism of GRK5 mediated receptor phosphorylation.

The SURF student will work with a postdoctoral fellow in the lab and learn protein purification and high-throughput crystal screening, and if sufficient progress is obtained crystal condition optimization and X-ray diffraction data collection.