Duke University | Chemical Biology Program

Enabling small molecule approaches to biological discovery.

Education

Small molecules provide a powerful means by which to probe – and ultimately to manipulate – biology. The Center for Chemical Biology takes seriously its responsibility to expose students at all levels and in myriad disciplines to the power of small molecule approaches.

At the undergraduate level, the Center for Chemical Biology has developed a new freshman chemistry course that considers the fundamental chemical concepts of freshman chemistry – structure and chemical bonding, thermodynamics and equilibrium, acid-base chemistry and kinetics – in the context of human disease. This advanced one-semester freshman course, available only to students who scored a 4 or 5 on the Advanced Placement Chemistry Test, begins with a review of cell cycle and the means by which control is exerted over cellular replication, especially phosphorylative control of replication. The failure of this control leads to disease, in the most significant manifestation to cancer. Students consider both covalent and non-covalent structure, ligand binding and equilibrium, protonation states and acid-based chemistry, kinetics and catalysis, all in the context of chronic myelogenous leukemia and the discovery of Gleevec™, the first targeted therapeutic for the treatment of a human cancer.

The world continues to shrink, and physical distances become less and less meaningful. Asia continues to emerge as a scientific powerhouse, a development that will pay enormous dividends for science. The Duke University Medical Center has worked closely with the National University of Singapore to develop a new Graduate Medical Center in Singapore. The Center for Chemical Biology is now working with faculty and administrators at GMS to develop an undergraduate Summer in Singapore experience. This unique opportunity will allow a selected group of Duke undergraduates to study in Singapore, discovering the power of chemical biology and how fundamental discoveries in chemical biology are translated to novel therapeutic agents.

At the graduate level, the Center for Chemical Biology offers a certificate program in Chemical Biology. The certificate recognizes a significant understanding of the approaches of chemical biology and the use of those approaches to understand important processes in biology. To receive certification, students require project approval by the Director of Graduate Studies and completion of a series of didactic courses designed to ensure grounding in the fundamentals of the discipline. Students considering certification are urged to contact the DGS early in their careers at Duke to ensure timely completion of program requirements.

Didactic Coursework

A list of seven didactic courses – in physical organic and synthetic organic chemistry, chemical biology, the structure of biological macromolecules, cell & molecular biology, and pharmacology – defines the core competencies required of all students in the program. The vast majority of trainees considering certification will have received didactic instruction in some, but not all, of these areas, and such students will place out of at least some of these courses. With the Director of Graduate Studies and the thesis mentor, each trainee will design a course of didactic study appropriate for both the student's undergraduate background and proposed thesis research.

Physical Organic Chemistry (CHM 331)

Bonding and structure, stereochemistry, conformational analysis, linear free energy relationships, substitution, addition, and elimination reactions, carbon reactive intermediates, concerted reactions, photochemistry, carbon alkylation, carbonyl addition, nucleophilic substitution, electrophilic additions, reduction, cycloadditions, rearrangements, main group organometallics, oxidation.

Essentials of Pharmacology and Toxicology (Pharm 233)

Principles of drug and toxin action, including pharmacokinetics, and receptor-mediated cell signaling.

Structural Biochemistry (BCH 258/259)

Introduction to the principles of macromolecular protein structure and function. Examples of methods of structure determination. Structure/function analysis of proteins as enzymes, multiple ligand binding, protein folding and stability, allostery, protein-protein interactions.

Modern Techniques in Molecular Biology (CMB 297; half-course)

Techniques for protein purification and analysis, and for the study of protein-protein interactions. Molecular biology, including discussions of nucleic acid sequencing and manipulation, cloning strategies, vectors, expression, hybridization and blotting methods, PCR, etc.

Macromolecular Synthesis (CMB 247; half-course)

The macromolecular synthesis course covers basic mechanisms of DNA synthesis, RNA transcription, protein translation, and protein stability.

Organic Synthesis (CHM 332)

Synthetic design, retrosynthetic analysis, synthetic methods, total syntheses.

Chemical Biology (CHM 339)

The use of concepts and methods of chemistry, especially small molecules, to solve problems in molecular and cell biology. The course is organized following the information transfer in biological systems, and emphasizes how chemists can intervene at each step, both to elucidate and control that flow. A major goal is to provide students with relevant background on useful chemical tools and new biological targets. Topics include the chemical synthesis of biological molecules (DNA, RNA, peptides, proteins, carbohydrates, lipids); recognition and modulation of DNA, RNA, and proteins with small molecules; application of small molecules in cell and developmental biology; basics of cell biology, forward and reverse chemical genetics, combinatorial chemistry, molecular target identification, and examples of small molecule application in cell biology.

Statistics for Basic Biomedical Scientists. (Pharm 333)

The use and importance of statistical methods in laboratory science, with an emphasis on specific aspects of experimental design, hypothesis testing, and statistical inference. Central tendency and dispersion, Gaussian and non-Gaussian distributions, parametric and nonparametric tests, uni- and multivariate designs, ANOVA and regression procedures.

Beyond the first year, students will take one or two additional courses based on the direction of their thesis research. A large number of courses are available for students to select from. Representative courses of special interest to program students include:

Interdisciplinary Approach to Pharmacology (Pharm 234/235)

The molecular, biochemical, and physiologic basis of drug action considered in the context of various model systems, including cancer, immunological disorders, and infectious diseases.

Cellular Signalling (Pharm/BCH/CB 417)

Mechanism of action of hormones at the cellular level including hormone-receptor interactions, secondary messenger systems for hormones, mechanisms of regulation of hormone responsiveness, regulation of growth, differentiation and proliferation, mechanisms of transport and ion channels, stimulus sensing and transduction. Some lectures stress the clinical correlation of the basic course concepts.

Biological Chemistry: Mechanistic Enzymology (CHM/BCH 336)

Basic enzymology, mechanisms of enzymatic reactions, cofactors, oxidoreductases, C1 chemistry, carbon-carbon bond formation, carboxylation/decarboxylation, heme, pyridoxal enzymes, thiamine enzymes.

Microbial Pathogeneis (MGM 282)

Modern molecular genetic approaches to understanding the pathogenic bacteria and fungi. Underlying mechanisms of pathogenesis and host-parasite relationships that contribute to the infectious disease process.

Virology and Viral Oncology (MGM 252)

Basic principles of viral structure and replication, the use of viruses as models for eukaryotic cell function, and the role of viruses in disease.