Testing computational re-designs of critical protein folds in epigenetic silencing.
Bassem Al-Sady, Professor
UC San Francisco
Applications for Fall 2026 are closed for this project.
A family of small protein folds contains a binding pocket ("aromatic cage") that is conserved through eukaryotic life and recognizes chemical modifications to chromatin, the packaging material of DNA. These small folds can execute several additional functions, like nucleic acid binding, that appear critical to how epigenetic silencing is carried out. However, it has not been possible to predict those functions from sequence and to assess what the contribution of the aromatic cage alone is to the establishment and maintenance of silencing. Together with the Kortemme lab at UCSF, we have redesigned such a model protein fold from scratch using computational protein design. In this project, we will test the functionality of these domains.
Role: The student will clone and express model re-designs of a histone H3 lysine 9 trimethylation–binding protein fold. This involves recombinant expression in bacteria, protein purification, and assays to determine peptide binding, nucleic acid binding, and oligomerization. The learning outcome will be to learn recombinant protein expression, fluorescence polarization, and protein crosslinking, along with associated molecular biology and protein biochemistry techniques. The student will also learn general scientific reasoning and data interpretation.
Qualifications: Ideally, protein biochemistry and recombinant expression. General molecular biology and biochemistry knowledge, like runnign DNA and protein gels, is preferred.
Day-to-day supervisor for this project: Farzad Yousefi
Hours: 12 or more hours