Consortium
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| Partner Name | Country |
| Dundee University | United Kingdom |
| LIONEX GmbH | Germany |
| Karolinska Institutet | Sweden |
| University of St. Andrews | United Kingdom |
| mfd Diagnostics GmbH | Germany |
The Participants
Dundee University
Division of Biological Chemistry and Drug Discovery
The Division of Biological Chemistry and Drug Discovery is one of the largest divisions in the internationally renowned College Of Life Sciences in Dundee. Our Division actively promotes interdisciplinary science mixing biology, biochemistry, bioinformatics, synthetic chemistry and structural biology mainly in areas related to medical microbiology.
The establishment of the Drug Discovery Unit funded by the Wellcome Trust, the Wolfson Foundation, Scottish Funding Council, European Regional Development Fund and University of Dundee has created a unique entity within Europe; the recruitment of staff with >120-yrs worth of industrial experience merging with the established academic excellence all supported by state-of-the-art instrumentation.
The Division is, together with colleagues at St Andrews, a founding member of the Scottish Structural Proteomics Facility, a focused and highly successful structural proteomics initiative exploring enzyme structure and function.
Main Tasks within the Project
Dundee University will be the Project Coordinator and responsible for overall management of the Project including communication with the Commission.
Our main research involvement will be to
• Lead the assessment and prioritization of targets from Gram-ve bacterial genomes and the knowledge management of the structural data produced by the work programs (WP-3)
• Carry out structure-based screening (WP-4).
• Enable an appropriate throughput of compound assessment for both drug discovery-based hit finding/lead development and chemical tool identification (WP-5)
• Perform Target-ligand characterisation (WP-6)
• Lead the dissemination and exploitation activities (WP-8)
People
Prof. William (Bill) Hunter has 25 years experience with X-ray structure determination and functional characterization of macromolecules. He has in excess of 120 Protein Data Bank entries with over 160 publications. He is a Fellow of the Royal Society of Edinburgh, the Royal Society of Chemistry and the Academy of Medical Sciences. He has held prestigious fellowships including for 10 years a Wellcome Trust Senior Fellowship. His research funding supports structural enzymology, inhibitor discovery for the DOXP pathway, trypanothione biosynthesis and glycophosphatidylinositol assembly.
Dr. Ruth Brenk is a recently appointed Lecturer. Her research includes study of interactions of small molecules with macromolecules by combining biophysical methods with computational chemistry. She is responsible for compound libraries, virtual screening campaigns and structure-based lead structure optimization. She has worked in world-leading structure-based ligand design groups; Prof. Brian Shoichet (USF California, USA) supported by a fellowship from the Ernst Schering Research Foundation. As a Ph.D. student with Prof. G. Klebe (Philipps Universität Marburg, Germany) she designed inhibitors of the enzyme tRNA-guanine transglycosylase with nM binding affinities and determined crystal structures of the complexes.
Dr David Gray is Head of Biology (since May 2010). He is responsible for the continuing development of an industry-standard ‘Hit Discovery’ Facility within the Division to support drug discovery for neglected disease and small molecule proof-of-concept for novel drug targets and pathways across a variety of indications. Previously, he was Director of Screening and Compound Profiling at GlaxoSmithKline with leadership of a unit supporting around 50% of GlaxoSmithKline’s European drug discovery portfolio (29 staff located in the Harlow Discovery Research Automation Facility Building engaged in molecular pharmacology, biochemical and cell based compound profiling, high throughput and developability screening support for phenotypic, kinase, GPCR, integrin, nuclear receptor and ion channel drug discovery programmes).
Prof. Andrew Hopkins designed a new class of anti-HIV agents during his doctorate research at the University of Oxford which were developed to drug candidates by Glaxo-Wellcome. He worked for 10 years, latterly as Head of Chemical Genomics, at the Sandwich site of Pfizer Global Research. In October 2008, he relocated to Dundee University as Chair of Chemical Informatics. He is the winner of the 2007 Corwin Hansch Award for SAR development. His work has involved the design and construction of major informatics systems, including a literature-mining system and a large-scale chemogenomics knowledge-base. He holds 7 patents covering a diverse range of inventions, including compound design, protein engineering and informatics systems.
Mr Vincent Rao is experienced in protein crystallisation and ligand binding assays and will be driving hit discovery against selected targets.
Dr Mary Gardiner will be developing high throughput assays and performing compound library screens for selected targets.
Sharon Shepherd has experience in protein purification (both in industry and at Dundee University) and will be cloning, expressing and purifying target proteins.
Dr Stuart McElroy was a founding member of staff at the Dundee Drug Discovery Unit and has spent three years working in screening from assay development through to lead optimisation. He will be conducting assay development and performing screening campaigns for selected targets.
For more information on our Division go to http://www.lifesci.dundee.ac.uk/bcdd/ and the Hit discovery group see http://www.drugdiscovery.dundee.ac.uk/shdf/overview/
Lionex GmbH
LIONEX is a growing biotech company with exceptional commitment to the problems of human and veterinary diseases such as TB, bovine TB and HIV infection. It is a partner of BioRegioN, a highly active biotech oriented region in Germany. LIONEX has excellent facilities and expertise in recombinant DNA technology, molecular biology and genetics, production of high quality, recombinant proteins for research and diagnostics. More than 100 recombinant proteins of M. tuberculosis have already been produced by LIONEX and are available in significant quantities. Several of the LIONEX products are currently in development as therapeutics for Cancer, Atherosclerosis and Asthma. The company is currently the Coordinator of two EC projects NEW TB Drugs and FASTEST-TB.
Main Tasks within the Project
The main research involvement will be to lead the genetic validation of targets (WP-1).
People
Prof. Mahavir Singh has been engaged in research on bacterial genetics since 1975 involving E.coli, Enterobacter, Azuspirillum, Salmonella, Shigella, Corynebacterium and Mycobacteria. He has supervised research projects funded by the WHO, European Commission, German Science Foundation and German Government. Prof. Singh is involved in national and international research projects on TB, HIV, Asthma and mycobacterial genetics.
Dr. Ralf Spallek is an expert microbiologist and has considerable experience in characterisation of targets.
Dr. Wulf Oehlmann has several years of experience in gene cloning, mutagenesis and handling of pathogenic organisms. He is also responsible for strain characterisation and cell banks.
Dr. Fatima Jonas and Dr. Susanne Kaempfer are experts for ELISAs and rapid test development and evaluation.
For more information on LIONEX see http://www.lionex.de/
Karolinska Institutet
Karolinska Institutet is the medical university of Stockholm, with a strong focus on medical/biomedical research. Karolinska Institutet, with a staff of approximately 2500, is one of the leading medical universities in Europe, and awards annually the Nobel prize in medicine and physiology. The department of Medical Biochemistry and Biophysics focuses on the structure and function of proteins, including their role in biological processes and disease. The department is dedicated to structural proteomics, directed towards human proteins, human pathogens and antibiotic biosynthesis. The structural biology laboratories have set up a high-throughput platform for protein production and crystallization including
- target selection and annotation
- gene cloning, expression screening, protein production and characterization (including MS, DLS, CD and thermofluor analysis)
- automated crystallization screening including crystal imaging and recognition and
- automated structure determination methods.
Main Tasks within the Project
Our main research involvement will be
• In the production of soluble proteins, their biochemical/biophysical characterization and structure analyses (WP-2).
• to lead the identification of novel ligands for targets employing Fragment Screening (FS) methods (WP-4).
People
Prof. Gunter Schneider has long-standing experience with X-ray structure determination and functional characterization of biological macromolecules, for instance the laboratory has determined in excess of 40 de novo structures of proteins. On-going research includes the structural enzymology of polyketide antibiotics, development of novel inhibitors against Mycobacterium tuberculosis and the structural basis of recognition and signaling in immunology and inflammation. Gunter is a member of the prestigious Nobel Assembly at the Karolinska Institutet and provides input to a number of important committees at National and International levels.
Dr Robert Schnell has experience in molecular biology, biochemistry and crystallography.
Dr. Tatyana Sandalova has experience in crystallography and bioinformatics.
Dr. Jason Schmidberger is an experienced structural biologist with a background studying enzymes and their reaction mechanisms. He will be working on the structural and functional characterization of target proteins.
Dr. Cyprian Cukier has experience in structural biology and biochemistry. Cyprian’s goal is to structurally and functionally characterize the target proteins which are involved in lipid metabolism.
Mr. Ahmad Moshref is a Technician in expression screening/protein production.
For more information on the Karolinska Institutet see http://phillips.mbb.ki.se/
University of St. Andrews
St Andrews University is Scotland’s oldest University founded in 1410. Despite its small size the University has an international reputation in humanities and the sciences with strong links across Europe in all academic disciplines. St Andrews has strong Institutional links with Dundee University. For example, with a block allocation of synchrotron time at ESRF and Diamond.
The Centre for Biomolecular Sciences brings together chemists and biologists, who work side-by-side with a focus on infectious diseases. The Scottish Structural Proteomics Facility (SSPF) automated core at St Andrews is supported by BBSRC and the Scottish Funding Council. The facility has automated cloning facility and high-throughput protein production equipment. It has state-of-the-art nano-dispensing crystallization robots and imagers. The lab has dedicated mass spectrometry support (whole protein and digested fragments). The lab uses CD, ITC and thermofluor analysis to characterize proteins.
Main Tasks within the Project
Our main research involvement will be in
• Lead the characterization of novel targets, production of soluble proteins, biochemical/biophysical characterization and structure analyses (WP-2).
• Contribute to structural analyses of fragment-target complexes (WP-4).
People
Prof. James Naismith has long-standing experience with X-ray structure determination and functional characterization of biological macromolecules. He has reported over 50 new protein structures, including a new class of membrane protein. Current work in the lab focuses on the mechanism of export of carbohydrates by Gram-negative bacteria, novel chemical mechanisms in bacteria (including Pseudomonas). Jim is a Fellow of the Royal Society of Edinburgh and the Royal Society of Chemistry.
Prof. Malcolm White is a biochemist and enzymologist with an interest in proteins and enzymes that interact with nucleic acids. He has discovered and characterized new DNA binding and repair proteins in thermophilic archaea, and works closely with structural biologists to explore protein structure:function relationships. He has many years experience in recombinant protein expression and purification. Malcolm is a Fellow of the Royal Society of Edinburgh.
Prof. Garry Taylor is a structural biologist of long standing. He has interests in computational aspects of crystallography and the structural biology of viral and bacterial proteins. He has developed a program of fragment discovery on neuraminidases (target in the treatment of influenza). This has lead to novel compounds being identified as drug candidates. Garry is a Fellow of the Royal Society of Edinburgh.
Dr Stephen McMahon is an experienced crystallographer and will be working on new structure determinations.
Dr Lucille Moynie has recently moved from Bordeaux to join the consortium studying new structures and ligand complexes.
For more information on the Centre for Biomolecular Sciences at the University of St. Andrews see http://biology.st-andrews.ac.uk/cbms/staffProfileResearch.aspx
mfd Diagnostics GmbH
mfd Diagnostic GmbH intends to become a leading product and service
provider for all institutions dealing with proteomics or phenomics, interested to increase security and to reduce costs, time, and the number of animals needed. The company’s concept is to be a one-stop-shop offering four interlinked platforms settled around the focus of in vivo / ex vivo compound screening for specific disease models.
1. Diagnostics
2. Antibody and Assay development
3. Contract research
4. Bio-techniques
Main Tasks within the Project
Our main research involvement will be realisation of in vivo studies (WP-1).
People
Dr. Bernd Lecher is a veterinarian with expertise in toxicity studies,tumor modeling, metabolism studies and surgical techniques approval. He is CEO of mfd diagnostics GmbH and responsible veterinarian of the internal animal facility including a spf housing area. Dr. Lecher is member of the GV-SOLAS (German society for animal research within the FELASA ) and TVT (German society for animal welfare).
Dr. Marko Maringer is a trained biologist with background in genetics,biomedical research and GLP based studies. As study director for GLP studies, he leads the contract research department of mfd diagnostics GmbH. Dr. Maringer is member of the DGPT (German society for toxicology and experimental pharmacology) and DGGF (German society for good laboratory practice).
Dr. Carmen Huck is biologist with background in immunology and molecular biology. She has experience in the development of diagnostics and therapeutics in cancer research and autoimmunity. As project manager she is responsible for the coordination of this study at mfd.
For more information on mfd Diagnostics see http://www.mfd-diagnostics.com/ .