First Name
Luke
Last Name
McAlary
Position
Postdoctoral Fellow
Office Room
Hennings 404B
Tel (Office)
(604) 822-3816
Email
lmcalary@phas.ubc.ca
Students Wanted
N/A

Bachelor's Degree
Univeristy of Wollongong, Wollongong Australia, 2011, B.Sc in Biotechnology

Citizenship
Australian

Research Area
Biophysics

Research Field
Cell and Molecular Biology

Research Topics
Protein folding/misfolding and aggregation, Proteostasis, Native mass spectrometry of proteins.

Abstract

Amyotrophic lateral sclerosis (also known as motor neuron disease) is a devastating neurodegenerative disease in which motor neurons specifically degenerate leading to paralysis and death. The majority of cases are sporadic (90%) where there is no discernable cause, the remaining cases are termed familial due to mutations being identified and linked to the disease in several different genes. One such gene encodes the protein superoxide dismutase-1, an enzyme that scavenges superoxide in the intracellular millieu and converts it to less toxic substances. Surprisingly, mutations in SOD1 don't cause ALS through a loss of function, but rather through a toxic gain of function. The toxic gain of function is considered to be associated with the impaired folding of the protein leading to generation of misfolded conformations and protein aggregates.

I seek to understand the process of SOD1 (and other proteins) misfolding, aggregation, and pathological spread, so that effective therapeutics can be generated to halt the progression of ALS/MND.


Selected Publications

McAlary L, Aquilina J.A, Yerbury J.J (2016), Susceptibility of mutant SOD1 to form a destabilized monomer predicts cellular aggregation and toxicity but not in vitro aggregation propensity, Frontiers in Neuroscience 10, http://dx.doi.org/10.3389/fnins.2016.00499

Whiten D.R, San Gil R, McAlary L,  Yerbury J.J, Ecroyd H, Wilson M.R (2016) Rapid flow cytometric measurement of protein inclusions and nuclear trafficking, Scientific Reports 6doi:10.1038/srep31138

McAlary L, Yerbury J.J, Aquilina J.A (2013), Glutathionylation potentiates benign superoxide dismutase 1 variants to the toxic forms associated with amyotrophic lateral sclerosis, Scientific Reports 3doi:10.1038/srep03275