Cryo-electron microscopy studies of DNA methylation complexes
Eva Nogales, Professor
Molecular and Cell Biology
Closed. This professor is continuing with Spring 2024 apprentices on this project; no new apprentices needed for Fall 2024.
DNA methylation at CpG sites plays an essential role in maintaining genome stability and regulating gene expression and it is strictly monitored and controlled by a series of molecular machines. Defects in DNA methylation are frequently found in severe diseases, such as cancer and Alzheimer's. DNMT1(DNA methyltransferase 1) with the help of UHRF1(Ubiquitin-like, containing PHD and RING finger domains 1) can be recruited to the DNA replication site and methylate the target loci. Despite intense study, the structure of the complex of DNMT1-UHRF1, and their interaction with nucleosomes are still unknown. Thus, it is still unclear how UHRF1 interacts with a nucleosome through its multi histone reader domains, how it recruits DNMT1, or how DNMT1 methylate DNA in the context of a nucleosome. Our goal is to answer these questions using cryo-EM.
Role: The DNMT1-UHRF1 project will involve molecular cloning, protein purification, nucleosome reconstitution, and high-resolution cryo-EM structure analysis. Advanced technology will be used for cryo-EM sample preparation, data collection, and high-resolution structure determination. Biochemistry assays will be performed to validate the cryo-EM findings.
Qualifications: Qualifications: Students with passion and enthusiasm for cutting edge research. The candidate is expected to have basic knowledge of biochemistry, such as molecular cloning and protein purification. Benchwork experience in biochemistry is preferred but not required. Ideally, the student commits to at least six months of work with the possibility of extension.
Day-to-day supervisor for this project: Zhenlin Yang, Post-Doc
Hours: 12 or more hours
Related website: http://cryoem.berkeley.edu
Biological & Health Sciences