西班牙圣帕布洛大学招聘神经学方向博士后

CEU San Pablo University (CEU) was founded in Madrid in 1993 and it is ranked as the second private university in Spain in research effort. CEU counts with 7 Research Centers, 40 research units and 11 research support services. Currently CEU is developing more than 50 research projects, with a budget that exceeds € 4 million. The University has an increasing history of collaboration with Industry, meaning around 65% of its R&D funding. CEU is looking for a highly motivated candidate to apply for a Marie Skłodowska-Curie Individual Fellowship - Postdoc position. Together with the selected candidate a MSCA IF proposal will be written and submitted. The involvement of the selected candidate in the proposal writing process will provide ample opportunity to tailor the proposal to his / her research interests. A successful application will result in a two-year appointment.
 

Description

Pleiotrophin (PTN) is a neurotrophic factor for dopaminergic neurons that is upregulated in the degenerating substantia nigra (SN) of patients with Parkinson’s disease (PD). Over-expression of PTN provides neuroprotection in animal models of PD. PTN binds to Protein tyrosine-phosphatase receptor Z1 (PTPRZ1) and inactivates its phosphatase activity, thus increasing the tyrosine phosphorylation levels of PTPRZ1 substrates. PTN is unable to cross the blood brain barrier. However, we hypothesize that PTN effects can be reproduced with rationally designed small molecule inhibitors of PTPRZ1 in order to validate PTPRZ1 as a new target for PD. The applicant will work in the synthesis of the only known inhibitor of PTPRZ1 and improved analogues designed through structure-based and ligand-based drug designs, using 3D-QSAR methods. The selectivity and potency of these compounds will be tested in vitro in a Protein Tyrosine Phosphatase activity assay, in order to determine their inhibitory effects on the phosphatase activity of PTPRZ1 and structurally-related phosphatases. Then, the applicant is expected to contribute to the pharmacological evaluation of the mentioned compounds. The applicant will participate in the test of the effects of the 3 most potent and selective inhibitors and PTN (as a positive control) against MPP+ induced loss of NGF-differentiated PC12 cell viability. The lead compound (lowest EC50 against MPP+) will be characterized in vivo for its pharmacokinetic properties. The applicant will have the opportunity to work with genetically engineered mouse models that will be treated with the lead compound in in vivo models of PD. In summary, fellowship holders will have the opportunity to participate in every step of an interdisciplinary project and will advance current knowledge regarding new pharmacological targets for PD.