Page 14 - Hormel Report 2021

Amer Alam, Ph.D.
“Visualizing the molecular details governing the proper physiological functioning of membrane proteins like ion channels, transporters, and receptors that constitute the overwhelming majority of pharmacological drug targets, helps us understand how their dysfunction relates to human health and disease, and can aid in development of better therapeutic and diagnostic tools for eventual
clinical utilization.”
Amer Alam
14 | THE HORMEL INSTITUTE // Structural Biology of
Membrane Transport
SECTION LEADER / ASSISTANT PROFESSOR
UNIVERSITY OF MINNESOTA
The Alam lab uses a combination of structural biology (cryo-EM and X-ray crystallography), biochemical, and cell
biological tools to study human ATP binding cassette (ABC) transporters. Members of family couple ATP hydrolysis to substrate transport and are involved in, among others, lipid and fatty acid metabolism and homeostasis, and cellular detoxification. Human pathologies associated with the function or dysfunction of these pro- teins include Alzheimer’s Disease, liver disease, X-linked Adrenoleukodystrophy and associated neurological impairments, and the development of multidrug resistance in cancer cells. We develop better in vitro models for studying these proteins through determining their high-reso- lution three-dimensional structures in multiple conformations embedded lipid reconstitution systems designed to mimic their native cellular
environments. Our goal is to 1) obtain funda- mental mechanistic insights into the function- ing of human ABC transporters, 2) understand how specific disease-causing mutations affect structure-function of select ABC transporters, 3) identify protein-protein, and drug-protein interactions, and 4) develop small molecule and antibody-based binders against our target proteins.
Our work is highly collaborative in nature and, as of August 2021, has been supported by a grant from the NIH National Institute on Aging as well as a foundation grant from
the adrenoleukodystrophy foundation.