Leveraging amino acid conservation, genetic variation in health and disease and gene expression to gain insight into pathomechanisms in the superfamily of voltage-gated sodium and calcium channels

• Applicant: Dr. Henrike Heyne
• Subject Area: Human Genetics ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 374360668

Voltage-gated sodium and calcium channels play a critical role in physiology and their malfunction has been associated with neurological, psychiatric, cardiological and other diseases. Respective pathomechanisms remain however poorly understood. Phylogenetic analyses have shown that the two gene families share a common ancestral gene, which is why they have many structural and functional similarities. By jointly analyzing the superfamily of voltage-gated sodium and calcium channels, we therefore gain statistical power. Specifically, we plan to develop a statistical model to identify sites where amino acids are more conserved than expected by chance across the superfamily. We then plan to map areas of amino acid conservation to i) protein domains, ii) results from electrophysiological tests as well as iii) variants from multiple large patient and control cohorts. We finally aim to integrate these results with gene expression data to gain insight into function and pathomechanisms of these highly disease-relevant proteins.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Mark Daly, Ph.D.