Watkins, Simon C |
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To join, leave or search the confocal microscopy listserv, go to: http://lists.umn.edu/cgi-bin/wa?A0=confocalmicroscopy ***** Postdoctoral Training Opportunity We are looking for a postdoctoral fellow to take on a project that is in full swing, but the current fellow doing the work is leaving for personal reasons. The project is perfect for someone who wants to learn and apply high end imaging approaches. The project combines multimode, high speed live cell imaging techniques with the development of a novel protein reporter method to study the function and cellular trafficking of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Mutations in the gene encoding CFTR are responsible for the genetic disease, cystic fibrosis, and proclivity toward other complex diseases, such as diabetes and pancreatitis. CFTR encodes a regulated anion channel that is required for the formation of epithelial apical secretions, being particularly important for an appropriate volume and composition of airway surface liquids in the lungs. The most common CFTR mutation omits phenylalanine at position 508 (F508del), which causes the protein to mis-fold, leading to its ER associated degradation (ERAD) and its failure to traffic to the plasma membrane where its function is required. However, optimal methods for detecting mutant protein rescue to the cell surface or its trafficking within intracellular pathways, have not previously emerged. Recently we have developed cutting edge high speed imaging methodologies that allow us to study the protein trafficking, in 3D in real time as protein is made, folded and migrates to the cell surface. The goal of these studies will be to use these approaches to perform basic cell biology studies, develop HTS assays and assess therapeutics. We are using the these imaging technologies to screen for small molecules that rescue trafficking of the mutant protein to the cell surface; a screen for CFTR correctors is just beginning. FAP-CFTR also permits the cellular trafficking patterns of wild-type and mutant CFTR to be assessed, as well as the action of secretory agonists and correctors on its cellular itinerary. In addition to reporting CFTR's cellular location, FAP-interacting fluorogens are available as reporters of the composition of cellular and near-membrane microenvironments (e.g. pH and calcium) in the vicinity of the tagged protein, permitting assessment of the impact of CFTR mutations on airway surface liquid composition. The development of these new tools will play a significant role in the development and success of therapeutic strategies for CF disease and potentially for other diseases affecting protein mis-folding and membrane trafficking. Qualifications of the applicant We are searching for a candidate with an extensive experience in cell biology. Experience in preparative molecular biology/biochemistry would be considered a plus, as well as experience in live cell imaging This is a multi-disciplinary project involving multiple people and excellent collaborative skills are therefore essential. Further, excellent communication skills in English are required. Qualified applicants are encouraged to send a copy of their CV and the names and contact details for three references to: Simon C. Watkins Ph.D, FRC Path Professor and Vice Chair Cell Biology Professor Immunology Director Center for Biologic Imaging BSTS 225 University of Pittsburgh 3500 Terrace St Pittsburgh PA 15261 412-352-2277 www.cbi.pitt.edu<http://www.cbi.pitt.edu> |
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