Molecular Signaling Pathways: How Genes Are Linked To Behavior
Prof. Richard C. Deth, Department of Pharmaceutical Sciences
Lecture Overview:
Within biological systems, the concentration of signaling
molecules represents a source of information for the
regulation of biochemical processes and electrical events.
Important categories of signaling molecules include hormones,
neurotransmitters and growth factors, each interacting with
specific receptor proteins that translate their concentration
into cellular effects. This lecture will review the molecular
basis for signaling via several of the major
receptor-initiated pathways, with an emphasis on the
structural features that provide for transmission of signals.
Signaling by the D4 dopamine receptor provides an interesting
example of how genetic diversity can influence a complex
behavior (i.e. the capacity for attention). Polymorphisms in
the D4 receptor gene found only in primates are associated
with novelty-seeking behavior and also with the risk of
attention-deficit hyperactivity disorder (ADHD). An
understanding of the unique features of this receptor, and
their role in signaling, allows a molecular hypothesis for
attention with implications for the origins of several
neuropsychiatric disorders.
Laboratory Overview
Molecular modeling, including 3-D molecular graphics, provides
a powerful technology for understanding molecular architecture
and assisting in the design of new drugs. In this laboratory
activity, students will be introduced to the molecular
modeling environment and will learn to use basic tools to
examine the structural features of signaling molecules,
including neurotransmitters, hormones and their respective
receptors and other relevant signaling intermediates. The
importance of molecular conformation and energetic
considerations in ligand-receptor interactions will also be
introduced.
Student Assigment
Students will determine the lowest energy conformation of
several neurotransmitters and prepare a brief report comparing
these conformations.