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Credit: 1 course unit
Elective course
Catalog description:
This course provides an introduction to the quantitative
methods used in characterizing and engineering biomolecular properties
and cellular behavior, focusing primarily on receptor-mediated
phenomena. The thermodynamics and
kinetics of protein/ligand binding are covered, with an emphasis on
experimental techniques for measuring molecular parameters such as
equilibrium affinities, kinetic rate constants, and diffusion
coefficients. Approaches for
probing and altering these molecular properties of proteins are also
described, including site-directed mutagenesis, directed evolution, rational
design, and covalent modification.
Equilibrium, kinetic, and transport models are used to elucidate
the relationships between the aforementioned molecular parameters and cellular
processes such as ligand/receptor binding and trafficking, cell adhesion and
motility, signal transduction, and gene regulation.
Prerequisites:
Senior BSE standing in BE or CBE – including
MATH 241, [BE 324 & BE 350 (as co-requisite) or CBE 350] – or permission
of instructor.
Textbook(s) and/or other required materials:
None required. All necessary materials will be
provided in class.
Recommended textbook (in
addition to those from the prerequisite courses):
D.A.
Lauffenburger and J.J. Linderman. Receptors:
Models for Binding, Trafficking, and Signaling. New York:
Oxford University Press, 1996. ISBN: 0195106636.
Course Objectives:
This course introduces the approaches that are
currently used for engineering biomolecular properties and how these
properties can, in turn, affect cellular phenomena. The focus is on quantitative
experimental methods and mathematical modeling of molecular and cellular
processes. By the end of the
course, students should be able to: identify crucial molecular parameters
involved in cellular events; understand how such parameters can be
experimentally measured or manipulated; and, formulate mathematical models
that incorporate these molecular parameters and appropriately capture the
salient features of the cellular phenomena being analyzed.
Topics Covered:
- Protein
biochemistry
- Energetics of
protein-protein interactions
- Equilibrium
and kinetic binding models
- Deviations
from simple monovalent binding models
- Experimental
methods for measuring constants and coefficients
- Protein
engineering
- Alanine-scanning
mutagenesis to isolate energetic “hot spots”
- Covalent
modification to alter diffusivity or association/dissociation rates
- Electrostatic
steering to increase association rates
- Directed
evolution to alter equilibrium affinity or dissociation rates
- Ligand/receptor
binding and trafficking
- Effect of
diffusion on receptor binding
- Models of
endocytosis, recycling, and degradation
- Cell adhesion
and motility
- Adhesion
strength per ligand/receptor bond (Bell model)
- Migration
models based on adhesion strength
- Leukocyte
rolling
- Signal
transduction
- Michaelis-Menten
enzyme kinetics
- Signal
initiation at cell membranes; Signal propagation and amplification
- Oscillations
- Adaptation
models
- Gene regulation
- Introduction
to non-linear dynamics, stability, and bifurcations
- Genetic
switches and cell cycle progression
Class/Laboratory schedule:
Lecture – 3 hr/week
Contribution towards Professional Component:
100% Engineering science
Contribution
towards Program Outcomes:
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Multidisciplinary
Ability
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High
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Problem Solving
Approach
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Med.
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Problem Solving
Methods
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High
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Experimentation
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High
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Design
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Low
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Professional
Orientation
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Med.
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Person preparing description and date:
Casim Sarkar
July 2007
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