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Biochemistry and Molecular Biotechnology Program

The Graduate Program in Biochemistry and Molecular Biotechnology offers graduate study and research focused in the areas of molecular, cellular and regulatory biochemistry, molecular biophysics, chemical biology, and structural biology.  Students receive a rigorous foundation in modern biomedical science through an integrated program of laboratory research, advanced coursework, and attendance and participation in seminar programs.  Students also organize and participate in a weekly informal seminar series in which they present recent research results.

Specific areas addressed within program laboratories include protein structure, function and evolution, regulation of gene expression, chromatin structure and epigenetics, translational regulation, membrane transport, ion channel function, drug resistance, cell cycle control, DNA replication, and neurodegenerative disease.

REQUIREMENTS FOR SPECIALIZATION

All Basic Biomedical Science students must complete the core curriculum as well as electives required by their program. Students in the Biochemistry and Molecular Biotechnology (BMB) program must take 3 graded elective courses of 2-4 credits each, two of which must be part of the BMB program course curriculum. The third elective is typically taken in Year 2; however, the student should enroll in a course (regardless of when it is offered) that is most relevant to their graduate research. The plan of coursework is designed to be flexible in order to accommodate each student’s needs and areas of interest.

All students in thesis research are required to give an annual research presentation to the Department in a seminar series that runs from September through May each academic year.

View PhD Program Schedule  |  View Courses

OUR LEADERSHIP & FACULY

PROGRAM DIRECTOR

Brian Kelch headshotBrian Kelch, PhD
Associate Professor
email Dr. Kelch  |  Learn more about the Kelch Lab

FACULTY

Our faculty include, Howard Hughes Medical Institute Investigators, W. M. Keck Foundation Distinguished Young Scholars, Burroughs Wellcome Fellows, Worcester Foundation for Biomedical Research Scholars, a Pew Scholar and a faculty member who patented discoveries in RNAi.

Research areas of our faculty inlcude:

  • Biophysics
  • Chemical Biology
  • Computational Biology
  • Cell & Developmental Biology
  • DNA/RNA & Epigenetics
  • Human Disease & Therapeutics
  • Membrane Biology
  • Neurobiology
  • Structural Biology

View the affilated faculty listing for the Biochemistry and Molecular Biotechnology Program.

OUR STUDENTS

The Graduate Program in Biochemistry and Molecular Biotechnology is an integral part of the Department of Biochemistry and Molecular Biotechnology.  Our graduate students are core members of our world-class research teams and a central part of our departmental culture.  Students organize our weekly departmental research seminar and happy hour, where they and other department members present their research.  They also present at our annual departmental research retreat, the university research retreat and at national and international meetings.  Many of our students are funded by NIH pre-doctoral fellowships and several have been awarded the prestigious Harold Weintraub award.

OUR STUDENTS IN THE NEWS

Getting Results…
  • PhD candidate Yvonne Chan a ‘protein engineer’
    Media, Research News

    PhD candidate Yvonne Chan a ‘protein engineer’

    In this Women in Science video, PhD candidate Yvonne Chan talks about her exploration of how proteins fold and maintain their three-dimensional structure.

    Read more

EXTERNAL AWARDS FOR RESEARCH TRAINING (CURRENT)

  • Magrino2.jpg

    Investigating sliding clamps and their contribution to genome stability

    All cells must replicate their genome once per cell cycle. To ensure proper duplication, cells integrate hundreds of factors that copy, surveil, and repair our genetic information. Proliferating Cell Nuclear Antigen [PCNA] and Rad9-Rad1-Hus1 [9-1-1] are ring-shaped clamps that act as master “conductors” that regulate many of the factors that replicate and maintain our DNA. PCNA is a homotrimeric ring that coordinates the replisome during DNA synthesis to work in tandem with DNA repair, chromatin remodeling, and cell cycle progression. When cells experience dsDNA breaks, they use the heterotrimeric clamp 9-1-1 to coordinate specific “SOS” repair factors. The collaborative efforts of both clamps are critical for genome stability. Many cancers are linked to inappropriate clamp coordination and changes in their expression. Because sliding clamps are central to many oncogenic pathways, we must address how they regulate themselves and their client partners. This proposal aims to address the following questions about sliding clamps: 1) How do sliding clamps coordinate their various partners? 2) Does the time sliding clamps spend on DNA influence genome stability? and 3) What determines site-specific loading of sliding clamps? I propose a multidisciplinary approach to address these questions about sliding clamps by investigating two-disease causing PCNA variants [PCNA-S228I [serine to isoleucine] and PCNA-C148S [cysteine to serine]] and the loading mechanism of 9-1-1. I hypothesize that sliding clamps control genome integrity via site-specific loading, proper partner interactions, and residence-time on DNA. I further hypothesize that PCNA-S228I and PCNA-C148S disrupt genome integrity by either promoting premature DNA dissociation or disrupting partner interactions. Finally, I hypothesize that the Rad17 subunit alters the clamp loader structure to specifically load the 9-1-1 clamp at sites of DNA damage. In aims 1 and 2, I will use PCNA-S228I and PCNA-C148S to address how clamps “choose” their partners and regulate their time on DNA. I will use x-ray crystallography, unfolding experiments, and a series of functional assays to determine how each variant compromises genome stability. In aim 3, I will determine the loading mechanism of clamp 9-1-1 to address how clamps are loaded to specific sites in the genome. I will use cryo-electron microscopy to determine how Rad17-RFC binds to clamp 9-1-1. Collectively, my work will broaden our insight into the factors that cause genome instability which may augment the development of personalized chemotherapeutics.

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POST-DEGREE CAREERS

Biochemistry and Molecular Biotechnology graduates pursue a variety of career options.  Many go on to postdoctoral training and subsequent academic careers.  Others pursue opportunities in the pharmaceutical industry and biotech, with recent graduates taking positions at Vertex, Biogen, Pfizer, Moderna, and Genzyme, among others.  Biochemistry and Molecular Biotechnology graduates have also pursued diverse career paths, such as law, publishing and policy.