Project Title: Cryo-EM Studies of the Parkinson’s Disease-Associated Protein LRRK2’s Normal and Pathological Functions
In this project I am utilizing cryo-EM and biochemical methods to address what interfaces within the LRRK2 protein are required to form its various oligomer states, such as trimers and MT-bound fibers. Using in vitro single particle methods I am answering how MT-binding by LRRK2 affects MT-based processes, and what role the different LRRK2 interfaces play in these effects. Finally, I am assessing in vivo neuronal phenotypes generated from disrupting the various interfaces and am answering whether the disruption of any interface can counteract the effects of known PD-associated mutations.
Mentors: Drs. Andres Leschziner and Samara Reck-Peterson, UC San Diego
Project Title: Exploring Interactions Between DNA Excision Repair Protein ERCC6 and RNA Polymerase Pol II for Cockayne Syndrome
In this project, we will study the interaction between ERCC6 and Pol II based on phylogenetic, structural, mutation, and simulation analysis. During the transcription, RNA polymerase II (Pol II) is the main player in the production of mRNA. However, Pol II may encounter obstacles during the transcription. DNA excision repair protein ERCC6 (also known as CSB) is among the first proteins to be recruited to the lesion-arrested Pol II, and help Pol II to overcome the obstacles and ensure the normal transcription process. Therefore, mutations in ERCC6 may cause severe autosomal disease, such as Cockayne syndrome. Our project will deepen our understanding of the ERCC6-Pol II interaction at the sub-molecular level.
Mentors: Drs. Ruben Abagyan and Dong Wang, UC San Diego
Project Title: Regulation of mTORC1 Signaling in Subcellular Compartments
This project aims to understand how mTORC1 activity is regulated in the nucleus and plasma membrane as well as to examine the cellular functions of mTORC1 in different compartments. We will combine chemical biology tool development, fluorescence imaging, biochemical interrogation and RNAseq technology to understand the regulation of specific pools of mTORC1. A computational structural biology approach will also be used to identify critical residues of mTOR and reveal new mechanisms of mTORC1 regulation by calmodulin.
Mentors: Drs. Jin Zhang and Wei Wang, UC San Diego