Mentor Areas
The ribosome, a molecular machine found in all living cells from bacteria to man, is responsible for translating messenger RNA into protein. However, it is more than a mere decoding and synthesizing machine. It is endowed with an exit tunnel, through which the newborn peptide moves as it is elongated. This tunnel, we are discovering, is not inert; rather it modulates protein folding. Among the earliest folding events in the biogenesis of a protein is the formation of a helix, an elementary structure that is ubiquitously present and required for correct protein folding in all proteomes. Protein folding inside the ribosome may even determine the fate of the newborn protein and whether it misfolds to cause pathological malfunction. The determinants underlying helix formation in the confined space of the ribosome are relatively unknown, and this proposal aims to fill in critical gaps in our knowledge of this biogenic modulation.
Description:
We have generated novel, testable hypotheses from functional studies, but now need to embark on a structural approach, namely cryo-electron microscopy, to visualize the nascent peptide and the tunnel. This is a totally new field of research for us and will generate pilot feasibility studies for an NIH application. The undergraduate will use peptide segments and novel biochemical assays to determine when a protein folds inside the ribosome to form a helix. First, we will test the hypothesis that secondary structure of a nascent peptide in the tunnel can be reconfigured by its emergent N-terminus. Second, we will determine whether different nascent peptides traverse idiosyncratic tunnel routes, which dictate their folding. These projects will establish new paradigms for peptide-ribosome interactions that govern folding mechanisms for all proteins to avert disease.
Preferred Qualifications
The student will learn the molecular basis of ribosomal translation, protein folding, and interactions between the nascent peptide and the ribosomal exit tunnel. Data analysis will provide the student with the skills required for quantifying protein gels. They will also present the results of their analysis at weekly lab meetings and be given research papers pertaining to the project to read and discuss.
Details:
Preferred Student Year
First-year, Second-Year, Junior, Senior
Academic Term
Fall, Spring, Summer
I prefer to have students start during the above term(s).Volunteer
Yes
Yes indicates that faculty are open to volunteers.Paid
No
Yes indicates that faculty are open to paying students they engage in their research, regardless of their work-study eligibility.Work Study
No
Yes indicates that faculty are open to hiring work-study-eligible students.