PhD student (f/m) within the TASPPI consortium
Development and implementation of HTS-applicable assays (HTRF, AlphaScreen, FP) for the identification of small-molecule PPI stabilizers from compound libraries.
Modulation of Protein-Protein Interactions (PPIs) with small-molecules is one of the most promising and challenging areas in Chemical Biology and Drug Discovery. Whereas inhibition of PPIs is meanwhile a well-documented and successful strategy, the opposite approach of small-molecule stabilization of PPIs has not been followed systematically. The adapter protein 14-3-3 acts as a “hub” by interacting with several hundred partner proteins in human cells. These 14-3-3 PPIs are implicated in a number of diseases ranging from cancer and neurodegeneration to inflammation and metabolic syndromes.
In the Innovative Training Network Targeted Stabilization of Protein-Protein Interactions (TASPPI), a Horizon 2020 MSCA-ITN-ETN project, we aim in a consortium of 5 universities (Dundee, Eindhoven, Leeds, Lille, Prague, Siena), 3 pharma companies (AstraZeneca, GSK, UCB), and 2 SMEs (Lead Discovery Center GmbH (LDC), Taros) to identify and optimize small-molecule 14-3-3 PPI stabilizers as novel tools for basic research and starting points for drug development.
The position described here is to be filled at Lead Discovery Center GmbH, Germany. The successful candidate (Early Stage Researcher, ESR) will work together with 12 other PhDs within TASPPI and will be included in a network-wide training and secondment program. As part of the MSCA mobility requirements candidates are eligible for this position when they have spent no more than 12 months of their main activity (work, study) in the last three years in Germany.
Thus, LDC is seeking for a PhD student (f/m) as a part of the before mentioned TASPPI project to perform:
Development and implementation of assays for High Throughput-Screening (HTS), cheminformatics, chemical optimization and pharmacology evaluation (ESR9)
The ESR will implement and perform HTS for the projects of the TASPPI consortium and identify validated hits that will be further optimized and profiled by use of Medicinal Chemistry and in vitro Pharmacology (evaluation of ADMET parameters).
The ESR will apply a broad spectrum of assay technologies as HTRF, AlphaSreen, Surface Plasmon Resonance etc. and will be intensively trained in the field of drug discovery.
The ESR will be additionally trained in project management at the interface of academic and pharmaceutical research, in patent searches and protection of intellectual property.
Dortmund, Germany (LDC)
6 months in Lille for NMR analysis of optimized compounds
Full time; for further details please refer to www.tasppi.eu
The position is open from 01.08.2016 and is concluded for 36 months
Required Degree and expertise:
M. Sc. in life sciences, e.g. biology, chemistry, biochemistry, pharmacology, pharmacy with a strong understanding of cell biology, biochemistry and organic chemistry.
Place of PhD Defense:
ESR will be enrolled in a PhD program at the University Eindhoven, Netherlands.
Students interested in cell biology and drug discovery, pharmaceutical sciences or related disciplines are invited to apply.
ESR 9 Supervisor at LDC
Bert Klebl, CEO & CSO at LDC, has gathered more than 15 years of professional experience in the life sciences/pharmaceutical industry. He has worked in different positions in drug discovery and early development. He is in his current role at LDC since early 2008. Most recently he was Senior Director Discovery Biology and Head of Biology at GPC Biotech. Previously he was Axxima’s Vice President Research and as such responsible for the discovery and development of the company’s portfolio of kinase inhibitors for various therapeutic indications. In former positions, he has worked as a project and platform manager primarily on a kinase inhibitor program, as well as a scientist at Aventis and Hoechst Marion Roussel. He earned his PhD in biochemistry at the University of Konstanz, Germany, and did postdoctoral work at the NRC Biotechnology Research Institute in Montréal, Canada. In the course of his research, he has published more than 30 articles in peer-reviewed journals and is a co-inventor of more than 20 patents and patent applications. He is scientific advisory board member of CI3, EMD and Vichem Kft. In addition he served as an expert panel reviewer for translation research centers, e.g. CDRD, Vancouver/Canada and IP-K, Seoul/South Korea.
LDC is a professional drug discovery company with all required infrastructure, core competencies and disciplines operating in a fully integrated way at highest industrial standards. The LDC is working closely together with its vast academic and industrial scientific network, e.g. the Max-Planck-Society, universities and pharmaceutical companies. LDC works closely with academic inventors to integrate their specific expertise and to draw on their unique tools, technologies, models, methods and materials. Collaborating with both academia and industry, LDC functions as a facilitator to translate academic basic research results into professional drug discovery projects and high quality products that can be readily commercialized. LDC offers the full workflow in early pharmaceutical drug discovery, including the indispensable disciplines lined out below and herewith covering all necessary technologies and equipment, ranging from drug design to sophisticated chemical synthesis and biological and pharmacological investigations.
The LDC consists of the four scientific departments Medicinal Chemistry (MedChem), Assay Development & Screening, Pharmacology and Biology. MedChem comprises analytical validation of hit compounds, selection of hits and post-HTS activities for hit-to-lead optimization, involving design, chemical laboratory work and medicinal chemistry based interpretation. MedChem includes parallel organic synthesis, computer-aided rational drug design, cheminformatics and computational chemistry analyses, design of focused compound libraries, design, synthesis and acquisition of analogs, establishment of structure-activity and structure-property relationships (SAR, SPR) and pharmacophore models, analoging activities, hit-to-lead identification based on biochemical or cellular active compounds, identification of active compounds, lead optimization. Assay development & Screening comprises development of biochemical and cellular assays for new targets and adaption of existing assays for MTS and HTS formats. LDC/HDC (HDC = “Hit Discovery Constance” which has been founded by LDC as subsidiary in 2011) provides large screening facilities including three HTS units (S2 approved Robocon/cellular uHTS system, Thermo CRS Dimension 4 system, CyBio System for biochemical assay based on fluorescence, luminescence and radioactive read-outs) addressing nearly all types of screening approaches. Biology comprises cellular pharmacology, evaluation of efficacy and toxicity, mode of action and phenotypic studies, cellular selectivity, identification of biomarkers and pharmacodynamic markers. Pharmacology comprises the assessment of chemical molecules, drug-like physicochemical properties, safety and efficacy of drug candidates, early ADME profiling, in vitro ADME screening, coordination and evaluation of PK-, PD- as well as metabolite studies, LC-MS based bioanalytics, coordination of in vivo efficacy studies and early toxicity studies.
LDC holds a profound track record of Target-to-Hit- as well as Hit-to-Lead optimization projects, as it performs numerous projects, e.g. together with the Max-Planck-Society. Moreover, LDC is partner in several projects funded by the European Union (ANTIFLU, FP7; Stabs14-3-3, Marie Curie, IAPP; ChemExit & HypoGreedy, Eurostars; EUC2LID, European Lead Factory, imi). LDC is involved/leading projects funded by the National German Government (BMBF: Lin28b eMed, Endoprotect; BMWi: ZIM AntiChlam) as well as projects funded by the Ministry of Science of North Rhine Westphalia (MWIF) (e.g. Emodi).
LDC has no indication focus but strong experience in the fields of metabolic disorders, cancer, inflammation and neurodegenerative diseases. Though LDC was founded in 2008, three lead packages were already licensed at commercially terms to Bayer Pharma and Qurient. Furthermore, LDC has strategic collaborations with Merck Serono and AstraZeneca on early stage projects.
While applying for the job please refer to jobvector and use the following reference number: LDC2016PhD ESR9
Lead Discovery Center GmbH
About Lead Discovery Center GmbH
Das Lead Discovery Center (LDC) wurde im Jahr 2008 durch dasTechnologie-Transfer-Unternehmen Max-Planck-Innovation (MI) gegründet, um das Potenzial exzellenter Grundlagenforschung auf der Suche nach neuen Therapien von Krankheiten mit hohem medizinischen Bedarf besser zu nutzen. Ziel des LDC ist es, aussichtsreiche Forschungsprojekte professionell in die Entwicklung innovativer...More about Lead Discovery Center GmbH