Probing receptor binding capabilities of mutant lynx modulators for better cognition and emotional processing.

Project Year: 

2017

Team Leaders: 

Julie Miwa, Ph.D. - Biological Sciences
Wonpil Im, Ph.D. - Biological Sciences
Frank Zhang, Ph.D. - Mechanical Engineering and Mechanics

Graduate Students: 

Kyung Min
Sang-jun Park
Jessica Willis

Undergraduate Students: 

Ryan Armbruster
Mark Crenshaw
Meaghan Gavey
Brooke Lichak
Megan Polak
Rachel Swope

Project Description: 

Anxiety disorders are among the most common mental disorders in the US but current methods to treat anxiety provide temporary relief and do not address the root cause.  We find that a protein LYNX plays a role in modulation of anxiety and is a good candidate as a novel target to alleviate anxiety. Several natural genetic variations to the lynx protein in humans, introduced by natural mutations in the gene, single nucleotides polymorphisms (SNPs), have been characterized. We predict that these mutations affect protein function, and thus an individual’s response to anxiety. 

We want to test this hypothesis by assaying the relevant mutations functionally. We aim to produce the normal SNP variants of the protein, and test their binding characteristics using atomic force microscopy (AFM) in cells expressing their cognate receptor, nicotinic receptors. We will also model computationally lynx/receptor interactions to understand the critical amino acids and the effect of SNP mutations on binding.

This project is interdisciplinary involving protein biochemistry, neuroscience, atomic force microscopy, computational modeling, and could also lead to more functional studies with electrophysiological and behavioral assays. These studies could provide a critical causal link between lynx and anxiety regulation, which could have a beneficial impact on human health and well-being.