news PS - Columbia University Medical Center

A look at work
from the labs
of CUMC’s
graduate
programs
Graduate life School
From Molecule to Disease
New drugs to treat disease are developed in two
general ways. Large scale screening involves
assessing the efficacy of an array of available
chemical agents against a disease proxy. In contrast, a
drug can be specifically constructed based on an understanding
of the underlying disease process. Often these
approaches overlap; some understanding of the disease
process can guide the selection of drugs for screening.
Several students in the Graduate Program in Pharmacology
and Molecular Signaling use sophisticated
techniques to examine at the molecular or even atomic
level the interactions between disease-related proteins
and ligands which bind to them, laying the groundwork
for the design of more potent and specific drugs.
Matt Le-Khac uses X-ray crystallography to assess
the interaction between HIV, the disease-causing agent
in AIDS, and small molecule ligands modeled on the
receptor to which the virus binds to gain entry to the
body’s immune system. (It was X-ray crystallographic
pictures of DNA that led Watson and Crick to their
epochal double helix model.) Matt prepares crystals
(regularly arrayed lattices) of the ligand bound to a
protein from the coat of HIV and takes them to a synchrotron
facility to bombard them with a high-powered
beam of X-rays.
The scattering pattern of the X-rays after collision
with the crystal yields information about the positioning
of atoms within the crystal, information that
By Daniel J. Goldberg, Ph.D.
Professor and Director
of Graduate Studies
Department of Pharmacology
The three-dimensional
structure of protein
enables researchers
to screen for ligand
interactions that may
be relevant to treatment
of disease.
ILLUSTRATION BY
ZACHARY WAYNE CARPENTER
Spring 2012 ColumbiaMedicine 29