The Department of Molecular Pediatrics, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-University, Munich, Germany offers the positions of
1 Postdoc (E13)
1 PhD (E13/2)
for a 3 years collaborative research project. The project is entitled "Identification of pharmacological chaperones for the treatment of the protein misfolding disorders phenylketonuria and medium-chain acyl-CoA dehydrogenase deficiency”.
Orphan genetic diseases are frequently associated with the phenotype of protein misfolding. Missense mutations lead to conformational destabilization and degradation of the affected protein eventually leading to a loss-of-function phenotype. For a number of diseases small molecule compounds (pharmacological chaperones) have been identified that bear the potential of conformational stabilization of the misfolded proteins. Our research of the past years focused on the molecular mechanisms behind protein misfolding disorders with loss-of-function phenotype, such as phenylketonuria (PKU) and medium-chain acyl-CoA dehydrogenase deficiency (MCADD). Moreover, our work contributed to the development of an approved pharmacological chaperone drug for the treatment of phenylketonuria. The current project aims to identify novel small molecule compounds with pharmacological chaperone efficacy for PKU and MCADD. In collaboration with biotech companies (Crelux, Martinsried; Nanotemper, Munich), the full sequence of high-throughput hit identification, functional validation, characterization of binding modes, and co-crystallization will be covered.
Applicants should have a background in biochemistry, chemistry, pharmacy or biology as well as good knowledge on methods of protein purification and protein biochemistry. Experience in structural biology is welcome but not mandatory.
We offer an academic working environment in a multidisciplinary team of physicians, chemists, and biologists. The project will cover aspects of both basic as well as translational research. The work in the laboratories of the children’s hospital in strong collaboration with biotech companies will provide in-depth insight into the process of drug development.
Soeren W. Gersting, MD