USA, Pennsylvania, Malvern

Position Summary:

Ubiquitin proteasome system (UPS) plays a fundamental role in human physiology and disease. The UPS system is responsible for removing damaged or misfolded proteins from cells. Dysfunction in UPS leads to cancer, inflammatory disorders, and neurodegeneration. The role of UPS in neurons is quite pronounced. Misfolded or aggregated proteins damage mitochondria, the energy factories of cells, loss of ATP in turn leads to death of neurons. Dysfunction or mutations in the master mitochondrial quality control ubiquitin E3 ligase Parkin, makes cells susceptible to neurodegeneration, such as Alzheimer’s and Parkinson’s diseases. Understanding the role of these mutations in E3 ligase structure and function will play a major role in early diagnosis of Parkinson’s disease (PD) as well as development of therapeutics. LifeSensors has established number biological assays to monitor E3 ligase function, its role in mitophagy, and mitobiogenesis.  Collection and functional annotation of all human gene variants will allow development of a Personalized Medicine and artificial intelligence platform that accurately simulates the resultant physiological consequences of protein variants.  The research scientist occupies a leadership position on a team developing novel PD diagnostics from UPS components in as well as characterizing drugs that target UPS for better neuronal health.

Requirements:

MS in Structural Biology, Computational Biology, Systems Biology, Genetics, Genomics, or similar discipline with relevant research experience. Industry experience is preferred but not essential.

• 0-2 years experience in analyzing protein structure data to evaluate protein variants, transcriptomics, proteomic and methods of generating and analyzing these data types will be required


• Proven track record of excellence in the analysis, visualization, and interpretation of genomic variants


• Scientific understanding of gene editing, the role of genetic variation in human disease, in cellular and structural biology


• Expertise with rapidly applying computational methods and bioinformatics tools to analyze protein variants and modeling the impact of variants on the structure of proteins


• Experience in biophysics, biochemistry, and structural biology is required


• Knowledge of the ubiquitin proteasome system is desirable but not essential


• Ability to apply software tools to model protein structure and function


• Write scholarly papers, patents and provide intellectual leadership for the company


• Communication, troubleshooting, and organizational skills

• Establish genomic data base of all parkin variants from public and private data bases


• Establish pipeline of a gene-to-structure using X-ray crystallography of E3 ligases and related proteins involved in mitobiogenesis


• Analyze structure by computational and biophysical approaches to simulate E3 Ligase structure function relationship


• Perform computational molecular modeling and simulations to accelerate the design and development of a high quality, novel small molecule that target E3 ligase


• Interact with experimental biologist to establish assays to validate genomic variations and its impact on the function of UPS enzymes and discover novel drugs


• Capture structural and genetic variations of mitophagy associated E3 ligase complex, apply biophysics, protein chemistry, and structural biology to process, analyze, and interpret data from a wide variety of sources to establish AI based platform to predict the role of E3 ligase variants in neuronal health