Chemistry-Biology Interface Training Program

Please check back in Spring 2020 for the next application cycle.

 

Program Overview

The Chemistry-Biology Interface (CBI) Training Program is an NIH funded training grant. The CBI represents an important cross-disciplinary area of training and research that encompasses the fields of chemistry, engineering, medicine, and pharmacy. Training will be conducted under the supervision of mentors with wide-ranging expertise in these research areas. Eligible trainees will enter the CBI program via one of four graduate programs: Chemistry and Biochemistry, Engineering, Scripps Institution of Oceanography, and Biomedical Sciences.

Events

 

Lecture Series

The La Jolla mesa is one of the world’s largest academic and industrial research centers, with an extraordinary concentration of chemistry, biology, chemical biology, and drug discovery and development efforts. This includes the academic institutions of UC San Diego such as Chemistry and Biochemistry, Division of Biology, Skaggs School of Pharmacy, Scripps Institution of Oceanography, UCSD Medical School, the Moores Cancer Center; the La Jolla Institute of Allergy and Immunology; the Salk Institute for Biological Studies; the Scripps Research Institute; the Sanford-Burnham Medical Research Institute; the J. Craig Venter Institute; and the California Institute for Biomedical Research. All of these institutes are within walking or biking distance of UC San Diego and each hosts its own seminar and symposia series, which offer seminars from world-renowned researchers from academics and industry.

Eight seminars per month will be recommended for the CBI Lecture Series, and students will be required to attend four. An online attendance checklist will be provided for the students and mentors to keep track of the seminars they attend.

Workshops

A monthly CBI Workshop will be provided as part of the CBI curriculum. This workshop will be held on the second Tuesday of each month from 12pm-2pm. All CBI students will be required to attend. All of the active trainers will also be required to attend.

The CBI Workshop will provide the trainees with a variety of personal, professional, scientific, and career seminars and activities to enrich their graduate experience. Workshops will consist of three different formats on a rotating basis:

  1. Research Progress Talks – Four workshops each year will focus on research progress. Here students will present 20 minute, formal PowerPoint style presentations that each allows 10 minutes of discussion.
  2. Journal Club – The students will select papers to read collectively and take turns presenting the research to others in the group, including background, strengths and weaknesses, and future directions.
  3. Grant Writing/Reviewing Exercises – The CBI workshop will incorporate grant writing and reviewing as an important element of the educational experience. Here the students will learn the basic elements of conceptualizing, organizing, writing, presenting, and judging research grant proposals. The project will occur in three phases:
    1. Phase I – Proposal Concept. Each student will individually prepare a grant proposal project, including a one-page Abstract, Specific Aims, and Timeline.
    2. Phase II – Concept Presentation. These concepts will be packaged into two (2) PowerPoint slides and presented to the entire group. The group will evaluate these proposals on the basis of NIH guidelines of Significance, Innovation, Approach, and Overall Impact. The top 50% of the Phase I exercise will be paired with a partner for Phase III.
    3. Phase III – Review. The review process will take place similar to an NIH Study Section. First, the reviewers will privately review the proposals along with the NIH guidelines of Significance, Innovation, Approach, and Overall Impact and provide a written evaluation. Next, a study section will be held, where the proposals are formally presented and reviewed for these criteria, and a priority score will be assigned. (Authors of the reviewed proposals will be in conflict and thus out of the room at the time of their review.) The students will be provided with the written Summary Statement, and the “funded” proposals will be announced.

Annual CBI Symposium

Each year, an annual CBI Symposium will be held in the summer, in which each trainee presents his/her research progress to the entire CBI group, which includes students and faculty. Each student will provide a written report of their research project one week before the CBI symposium. The faculty trainers will evaluate each student based on the written report, the presentation, and the Reflective Student Portfolio. Each student will briefly meet with the faculty to discuss performance and future directions.

Personal Career Guidance

A major component of the training program will be ongoing personal and career guidance. Mentoring will be conducted by the PI (Dr. Burkart) and the Executive Committee made up of mentors from the trainees’ home divisions: Chemistry (Gianneschi), Health Sciences (Gilson), Engineering (Christman), and Marine Chemical Biology (Moore).

Personal Guidance: Two tools will be utilized to enrich student learning and support throughout their graduate career: an Individual Development Plan (IDP) and a Reflective Student Portfolio (RSP).

An IDP is a self-conducted tool for the student to help them explore career possibilities and set goals to follow the career path that fits them best. The IDP is created by the student as a way to propose research and career objectives and to create milestones for their achievement. The IDP will further be used by the mentor of each student to fine tune each person’s training and research trajectory.

The RSP project for the CBI is designed as a career or professional portfolio that the student will initiate upon joining the CBI program, with the intention of keeping it up throughout their graduate career. This RSP will help the CBI students organize, track, store, and maintain any documents related to their training and career as a way to showcase their skills, experience, and samples of accomplishments.

In addition to the IDP and RSP, the Executive Committee together with the PI will provide additional career guidance to the trainees. This will culminate annually in a Career Day. Speakers will be invited to discuss the various career trajectories that are possible for the Ph.D. graduates in Chemical Biology. The Career Day will be a half-day event, with 6-8 presentations of 20 minutes, followed by 10 minutes of discussion, punctuated by coffee breaks and a social hour. Speakers will include individuals from academic, industry, intellectual property and government employment backgrounds. Representatives from local industry will be invited for opportunities to interview training program trainees on campus through the UCSD Career Services Center.

CBI Training Program Faculty

 

Executive Committee

Michael Burkart, PI Chemistry & Biochemistry

Karen Christman (Bioengineering)

Michael Gilson (School of Pharmacy)

Kamil Godula (Chemistry & Biochemistry)

Bradley S. Moore (Scripps Institution of Oceanography, School of Pharmacy)

Victor Nizet (School of Medicine)

Faculty Mentors

Ruben Abagyan (School of Pharmacy)
Structural bioinformatics, drug discovery, green chemistry, and study of the adverse effects of chemicals on human health.

Adah Almutairi (School of Pharmacy)
Development and design of polymers that fall apart in response to biological or external triggers to enable on-demand
drug delivery and disease-specific imaging agents.

Rommie Amaro (Chemistry & Biochemistry)
Computational chemical biology and biophysics

Timothy Baker (Chemistry & Biochemistry, Biology)
Macromolecular, cryoelectron microscopy and three-dimensional, image-reconstruction techniques especially pertaining to the elucidation of virus structures.

Michael Burkart, PI Chemistry & Biochemistry
Secondary metabolite biosynthesis and production leading to new approaches for drug discovery, renewable energy and biomaterials.

Karen Christman (Bioengineering)
Biomaterials for tissue repair and regeneration.

Seth Cohen (Chemistry & Biochemistry)
Inhibitors of metalloproteins for the development of therapeutics and the development of functional metal-organic framework structures.

Galia Debelouchina (Chemistry & Biochemistry)
Chemical and spectroscopic approaches for structural biology of complex biological systems.

Neal Devaraj (Chemistry & Biochemistry)
Bioorthogonal reactions and their use in molecular imaging and synthetic biology.

Pieter Dorrestein (School of Pharmacy)
Interrogation and classification of the therapeutically relevant proteins that are related to the biosynthesis of secondary metabolites, or are involved in the formation of post-translational modifications.

Adam Engler (Bioengineering)
Mechanobiology of stem cells, progenitor cells, and their progeny as well as cancer cells using methods borrowed from tissue engineering, biomaterials, cell and molecular biology, and genetics. 

Sadik Esener (NanoEngineering, Electrical & Computer Engineering)
Cancer nanotechnology and biophotonics.

William Gerwick (Scripps Institution of Oceanography / School of Pharmacy)
Marine Natural Products Drug Discovery and Biosynthesis

Nathan Gianneschi (Chemistry & Biochemistry)
Responsive, reactive chemical systems and materials in catalysis, sensing and in biomedical applications including targeted drug, gene and probe delivery in vivo.

Michael Gilson (School of Pharmacy)
Theoretical, simulation, and informatics approaches to molecular recognition, with applications in molecular design and drug discovery.

Partho Ghosh (Chemistry & Biochemistry)
Structural biology of host-pathogen interactions.

Kamil Godula (Chemistry & Biochemistry)
Nanotechnologies for analysis of glycan function during development. Glycomaterials for stem cell-based tissue regeneration.

Tracy Handel (School of Pharmacy)
Structure and function of chemokines and the GPCR chemokine receptors.

Stephen Howell (School of Medicine, Moores Cancer Center)
Ovarian cancer and platinum-based drug chemotherapy resistance.

Patricia Jennings (Chemistry & Biochemistry)
Uncovering the basis for the allosteric regulation of proteins by protein, metal and small molecule binding.

Elizabeth Komives (Chemistry & Biochemistry)
Biophysics of protein-protein interactions, with a focus on dynamics and functional consequences.

Alexis Komor (Chemistry & Biochemistry)
DNA damage and repair; Genome editing.

Robert Mattrey (School of Medicine)
Noninvasive imaging techniques for improved diagnosis and monitoring of treatment efficacy for atherosclerosis and cancer.

J. Andrew McCammon (Chemistry & Biochemistry)
Computational chemistry and biochemistry, including computer-aided drug discovery.

Tadeusz Molinski (Chemistry & Biochemistry, School of Pharmacy
Discovery of novel antiproliferative natural products from marine organisms, synthetic medicinal chemistry of proapoptotic small molecules, and chemical biology of natural product-ligand structures.

Bradley S. Moore (Scripps Institution of Oceanography, School of Pharmacy)
Biosynthesis of marine natural products, including pathway elucidation, enzymology, and metabolic engineering.

Victor Nizet (School of Medicine)
Bacterial pathogenesis and innate immunity.

Stanley Opella (Chemistry & Biochemistry)
Molecular and structural biology of proteins through advanced high resolution NMR techniques.

F. Akif Tezcan (Chemistry & Biochemistry)
New inorganic supramolecular approaches to control the in vitro and in vivo assembly of functional protein complexes.

Navtej Toor (Chemistry & Biochemistry)
Structural biology of RNA splicing.

Yitzhak Tor (Chemistry & Biochemistry)
Chemical biology of highly charged biopolymers, including nucleic acids and proteogylcans and their interactions with small molecules.

Shyni Varghese (Bioengineering)
Adult and embryonic stem cells, biomaterials, smart hydrogels, cell/matrix interactions, disease progression, tissue engineering, regenerative medicine

Dong Wang (Skaggs School of Pharmacy and Pharmaceutical Sciences)
Structural biology and molecular mechanisms of cellular responses to DNA modifications, particularly the functional interplay between transcription and epigenetic DNA modifications and lesions.

Liangfang Zhang (NanoEngineering)
Design, synthesis, and evaluation of nanostructural biomaterials for biomedical applications including drug delivery.

CBI Coursework

213A. Structure of Biomolecules and Biomolecular Assemblies

A discussion of structures of nucleic acids and proteins and their larger assemblies. The theoretical basis for nucleic acid and protein structure, as well as methods of structure determination including x-ray crystallography, cryoEM, and computational modeling approaches will be covered.

216. Chemical Biology (4) 

A discussion of current topics in chemical biology including mechanistic aspects of enzymes and cofactors, use of modified enzymes to alter biochemical pathways, chemical intervention in cellular processes, and natural product discovery. Prerequisites: graduate standing or consent of instructor.

Scientific Ethics

All trainees must complete a scientific ethics course. For Chemistry & Biochemistry Department students, this requirement is satisfied by the first year seminar taken in Spring, CHEM 250. For all other trainees, the ethics requirement can be fulfilled through any of the following campus course offerings: SOMI 226, COGS 241, SIO 273, SIO 232.

Application

Applications for the 2019 is now closed. Please check back in Spring 2020 for the next application cycle.

Current CBI Trainees

2019-19 Trainees

Raymond Berkeley 

Chemistry and Biochemistry
Galia Debelouchina Lab

Chemical tools for the study of intrinsically disordered proteins

Intrinsically disordered proteins (IDPs) play key roles in numerous cellular processes. These proteins often condense into discrete intracellular droplets that are required for these proteins to carry out their function. Despite the central role of these protein droplets in cell biology and disease, the mechanisms that underlie protein phase separation are poorly understood. The dynamic nature of these protein droplets makes nuclear magnetic resonance (NMR) the ideal tool for their study, but the low sensitivity of NMR makes it difficult to study IDPs in their native environment. Our lab uses dynamic nuclear polarization to circumvent the sensitivity problem. My work focuses on the design of probes that are capable of delivering polarization agents to intracellular protein droplets in order to selectively enhance the NMR signal from these condensed proteins. These probes will enable the study of the structural basis for phase separation in cells without requiring any chemical modification to the proteins under study.

Albert Kakkis 

Chemistry and Biochemistry
Akif Tezcan Lab

A metal-mediated path to biological materials: Harnessing coordination chemistry for heteromeric protein assembly

The self-assembly of proteins into multi-component supramolecular architectures underpins Nature’s most complex transformations, from nitrogen fixation to photosynthesis. Synthetic multi-component assembly is a long-standing goal of protein engineers, as it introduces a repertoire of functions unattainable via single-component assemblies. Current methods rely on the computational design of non-covalent interactions across large interfaces (>1,000 Å2), which limits the generalizability and reversibility of the designed assemblies. We aim to develop a method for multi-component assembly that can 1) Rely on minimal computational design, 2) Be achieved using small interfaces, and 3) Be externally controlled. To meet these criteria, we will use metal-ligand and π-π stacking interactions, popular tools in the design of small molecule assemblies that are underutilized in protein assemblies. As a proof of concept, we will harness CuII-tetrahistidine coordination motifs and π-π stacking interactions between nitroarenes and tryptophan to design a heterodimeric assembly of four-helix bundle proteins. Successful design of multi-component assemblies using these interactions would expand the chemical toolbox for de novo protein design. 

Kelsey Krug

Chemistry and Biochemistry
Michael Burkart Lab

Application of small molecule splice modulators

RNA splicing plays a central role in disease and cancer progression, but the complexity of this large-scale process has left the study of RNA splicing unexplored. Recently, the alteration of splicing by small molecule splicing inhibitors (SPLMs) has been identified as an avenue for chemical biological discovery. My project focuses on the combined use of splice modulators with other cell-cycle regulating clinical agents, Rigosertib and Alisertib, which inhibit polo-like kinase 1 (PLK-1) and aurora kinase (AK) respectively, to selectively control the expression of cell-cycle progression proteins. The goal of this effort is to combine a molecular and cellular understanding of cell cycle selectivity for splice modulation as a tool to enhance specific cell cycle events. This concept relies on the use of the splice modulator to downregulate the levels of PLK-1 and AK by altering their splicing, and then using the reduced levels of these proteins to enhance the efficacy of their associated inhibitors, Rigosertib and Alisertib. So far, I have looked for synergy between PLK-1 and AK inhibitors and the splice modulator FD-895 in G1-synchronized human colon carcinoma HCT116 cells. Using the MTT assay, I found that the combined use of FD-895 with Rigosertib or Alisertib led to reduced tumor cell proliferation compared to treatment with either compound on their own. This preliminary data indicates that splice modulation can affect cell cycle regulation. Next, I will use qPCR to evaluate PLK-1 and AK mRNA isolated from G1-synchronized HCT116 cells that have been treated with splice modulator FD-895, and then either Rigosertib or Alisertib.  By varying the treatment time with FD-895, I will determine an optimum length of treatment, the one that most reduces the levels of spliced PLK-1 and AK mRNA.

Brodie Ranzau 

Chemistry and Biochemistry
Alexis Komor Lab

Repurposing RNA-modifying enzymes for genome editing

Single-point mutations are the genotypic cause of the vast majority of genetic diseases. Genome editing is one method of treating genetic diseases by mutating the pathogenic allele into a healthy allele. Current genome editing techniques create double-stranded DNA breaks (DSBs) at target locations in the genome, which are recognized by DNA repair pathways that may incorporate a supplied DNA strand and lead to successful genome editing. This process is inefficient, especially when attempting to substitute a single base pair, and may create other harmful insertions or deletions at the DSB. My work aims to circumvent the use of DSBs by creating precision base editing tools that can chemically modify target nucleobases. Base editors capable of causing C-to-T and A-to-G mutations have already been created. By directing the evolution of RNA modifying enzymes, new base editors will be created that cover other modifications and mutations, vastly increasing the utility of these tools for editing the genome.

Ariana Remmel

Chemistry and Biochemistry
Kamil Godula Lab

Design and Synthesis of Glycopolymers to Assess Sperm Binding to Mucus Glycans

Cervical mucus (CM) is an important barrier in pathogen elimination and sperm selection during human reproduction. This mucus is a viscous network primarily composed of glycoproteins called mucins. Mucins are comprised
of a protein backbone highly decorated with glycan chains (80% per weight of mucin molecule). The viscoelastic properties of CM and its production volume change dramatically throughout the menstrual cycle such that CM is thin and copious during ovulation, but scant and thick outside of ovulation. This is believed to limit sperm transit to the ovulatory window. However, these rheological changes also correlate with altered glycan expression, with more sialic acids present outside of ovulation and increased fucosylation during ovulation. While the mechanical properties of CM have been well studied with respect to sperm penetration, little is known about sperm interactions with the changing glycans of CM. It is well known, however, that sperm bind to glycan partners in the female reproductive tract to both form the oviduct reservoir and penetrate the egg. Given the prevalence of glycans in CM, it would appear that sperm surface interactions with mucus glycans could also affect sperm selection by the female host. This project aims to create chemical tools to better understand the interactions of human sperm with CM glycans.

Holly Sullivan 

Bioengineering
Karen Christman Lab

Inhalation of polymeric nanoparticles for therapeutic delivery after myocardial infarction

Every year, nearly 800,000 people in American have a heart attack. Many of these patients will now be in heart failure— 5 million people are living with congestive heart failure, and on average they will die within 5 years of diagnosis. The mounting prevalence of heart disease related deaths creates the need for more efficient methods of treatment. Nanoparticles present a non-invasive, targeted method of delivering therapeutic small molecules and peptides to the infarcted region of heart post myocardial infarction (MI). Our work, in collaboration with the Gianneschi lab at Northwestern University, is aimed at developing degradable polymeric nanoparticles that localize in the infarct after being cleaved by matrix metalloproteinases that are upregulated after MI. The nanoparticles preferentially enter the infarct via the leaky vasculature and remain in the infarct following a morphological switch to micron-scale aggregates in response to enzymatic cleavage.  Inhalation of nanoparticles is highly translational and minimally invasive, making it a desirable form of administration moving forward.

Trainee Travel Guidelines

AWARD GUIDELINES:
– Only students appointed to the Training Grant are allotted these funds. 
– Maximum travel award is $300
– Reimbursement provided for registration, travel costs (i.e. airfare, mileage), and lodging.
– Submit the form as soon as possible before your travel, for tracking purposes. 
– Unused funds will be lost if not used by June 30th of each year. 

Contact

Program PI

Dr. Michael Burkart, Ph.D.

Department of Chemistry & Biochemistry
U.C. San Diego
La Jolla, CA 92093-0378
Phone: (858) 534-5673
Email: mburkart@ucsd.edu

Staff

Jeanine Sun

Graduate Program Manager
Phone: (858) 822-6014
Office Location: York 4010 (Revelle College)

Asmaa Khatib

Training Grant Program Coordinator
Phone: (858) 534-2263
Office Location: York 4010 (Revelle College) 
 
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