Michael Parsons Email and Phone Number

Generating and characterising genetic models of Muscle Disease:• Generated a functional 3D muscle model using primary myoblast lines to show that the reversal of the molecular phenotype leads to a corresponding rescue of the muscle phenotype.• Created immortalized genetic tool lines (isogenic lines, CRISPRa) using primary myoblasts to generate complementary functional models for validation and proof of concept experiments.• Conducted compound screens in primary myoblast cells using ICC and qPCR as functional readouts.

Generated and characterised genetic models of Kidney Disease:• Generated and characterized inducible, stable models of gene expression for use in assay development for drug screening and mechanism of action (MOA) studies.• Optimized expression constructs to ensure disease relevant expression levels while still maintaining a wide phenotypic assay window.• Determined the effect of gene overexpression on disease relevant phenotypes using transient transfection, lentivirus transduction, and baculovirus transduction.• Phenotypically characterized these lines for a range of cell death and cellular morphology measurements using a novel ICC pipeline (metaexpress).• Used CRISPR technology to generate genetic tools lines to add in assay development (KO lines, isogenic lines, recombinantly tagged lines). • For example, added a Hibit tag to a disease relevant gene be able to simplify and scale up a protein expression screening assay for this project.Conducting a primary neuronal assay for drug screening into neurological disease:• Ran a mixed, primary neuronal assay using a small molecule compound screen to aid in the lead optimization of a novel candidate scaffold. • Developed and conducted an siRNA screen of MOA candidate genes to aid in target discovery and mechanism of action studies.

Successfully obtained an independent NARSAD fellowship to develop and characterize models of sleep, circadian rhythms, and neurological disorders based on human GWAS data.• Prioritized candidate genes from human genome-wide association studies (GWAS), then screened domains of these genes in a DNA archive using a high-throughput PCR based assay to detect and verify novel mouse mutants.• Developed and optimized functional in vitro assays to characterize these mutations and to help prioritize which mouse mutations were rederived.• Following rederivation, conducted behavioral and quantitative molecular assays to identify the effects of these mutations, specifically as they related to the original GWAS phenotypes.Characterized the novel circadian mouse mutant Short circuit (in Zfhx3) as part of a forward genetics mutagenesis screen for circadian behavior. Published this work in Cell (2015) as lead author.• Discovered that the short circuit mouse mutant was caused by a mutation in a highly conserved region of transcriptional gene (Zfhx3). • Coordinated bioinformatic efforts to analyse RNA sequencing data and produce gene expression networks to better understand the mode of action of this Zfhx3 mutation.• Determined that the short circuit mutation led to an altered transcriptional profile that in turn affected the expression of key circadian genes. Used reporter gene assays and site-directed mutagenesis to determine the sequence specificity of the DNA elements differentially regulated by this mutation.• Verified Zfhx3’s function in vivo using transgenic mouse lines and RNA interference (siRNAs).Other responsibilities and projects:• Conducted genetic association studies (SPSS, STATA, R) to replicate human GWAS loci and detect unique genetic influences of circadian rhythms/sleep and psychiatric disorders in human samples.• Acted as laboratory manager planning, conducting and supervising numerous interdisciplinary projects.

• Developed and executed a systems biology project using complex mouse genetic populations (recombinant inbred lines) to use the naturally occurring genetic variation in miRNA genes to determine the roles that these genes have on both expression pathways and behavior (locomotor activity/gait, anxiety, depression and cognition).