Courses:

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The goal of this course is to provide a student with a view of how pathways network together to enable complex behavior or function. A series of topics are covered, some of which change from year to year, to illustrate the functioning of biological networks. The lectures present examples of complex pathways (chemotaxis, nitrogen fixation, lactation, cytokine mediated intercellular signaling, apoptosis, etc.). In each case emphasis is placed on how these pathways are regulated at the molecular, cellular and tissue levels.

There are two examinations during the course, which have the goal of preparing BE graduate students for their qualifying examinations. The principal product of the course is a student team-generated grant proposal. The topic this year is the design of experiments that probe unique aspects of the biochemical networks associated with apoptosis. Students prepare for their topic both out of class and in class during recitations (we plan to teach three hours per week and reserve about one hour for discussion). After each framing session, students go to the literature and flesh out their ideas as topics for a grant proposal. They present their ideas to the class in Power Point format during the framing sessions. After the ideas are fleshed out, the students jointly write their grant proposal. Each student writes a section of the proposal that is identified as their own.

Readings are in the form of primary scientific papers, reviews, and selected chapters from texts.

The proposal is written in the NSF format or in that used by investigators applying for a grant from the National Institutes of Health.

Course Description

Complex biological processes are analyzed from the molecular, cellular, extracellular, and organ levels of hierarchy. Emphasis is placed on the basic biochemical and biophysical principles that govern these processes. Examples of processes to be studied include chemotaxis, the fixation of nitrogen into organic biological molecules, growth factor and hormone mediated signaling cascades, and signaling cascades leading to cell death in response to damage. In each case, the availability of a resource, or the presence of a stimulus, results in some biochemical pathways being turned on while others are turned off. The course examines the dynamic aspects of these processes.

Building on a foundation of knowledge of pathway biochemistry (including kinetics and thermodynamics), we examine the molecular switches that dynamically trigger responses at the transcriptional, translational and protein-activity levels of control. While the objective of the course is not to teach about specific diseases, the course sometimes discusses diseases of animals or plants as teaching tools to understand how pathway disruptions can lead to readily observed phenotypes. Examples could include diabetes mellitus, mucopolysaccharidosis, ataxia telangiectasia, cystic fibrosis, cholesterol biosynthesis, hormone dependent cancers, and defective response to growth hormones in plants. Additionally, however, basic phenomena such as how concentration gradients trigger motion in the direction of or away from a stimulus are studied and, as appropriate, modeled. This course details how biochemical mechanistic themes impinge on molecular-cellular-tissue-organ level functions. Thus the goal is to provide a chemical and quantitative view of the interplay of multiple pathways as biological networks.

Course organization involves didactically taught classes dealing with the aforementioned topics, complemented by a class project. Early in the term, the class is brought up to the same level through analysis of topics not taught in detail in the MIT undergraduate biological chemistry courses. Nitrogen fixation into amino acids and nucleotides is covered as a thermodynamically highly favored, yet sluggish and energy consumptive, process that is central to all life. Only a few species of plants in symbiotic relationships with a few species of bacteria fix nitrogen. Nitrogen from ammonia is tracked into amino acids, affording the opportunity to refresh the student’s ability to use organic chemistry to work through a complex pathway. The mechanisms by which nitrogen fixation and introduction into organic molecules is regulated are emphasized. Amino acids are sometimes used as molecular attractants in chemotaxis experiments. The switch of bacterial motion from random to directional is analyzed. Other topics covered include the pathway by which lactation occurs, apoptosis, blood coagulation, intercellular trafficking, cell signaling, and others.

The following texts are used (but not required) and supplemented with readings from the primary literature:

Voet, Donald and Judith G. Voet. Biochemistry. New York, NY: Wiley, 2004. ISBN: 9780471193500.

Devlin, Thomas M. Textbook of Biochemistry with Clinical Corrections. New York, NY: Wiley, 2001. ISBN: 9780471411369.

One hour per week of class time is devoted to recitation.

A term project undertaken by subgroups of the class working as integrated teams involves the preparation of a unique grant application in an area of biological networks. The term grade derives from class participation, formal presentations in class and the written grant application.

This subject is restricted to graduate students enrolled for credit.

Grading