[ccp4bb] Position available
Posted on behalf of Christophe Verlinde. Please reply to him at the e-mail address below. POST-DOC STRUCTURE-BASED DRUG DESIGN IN SEATTLE Join a multi-disciplinary team (protein crystallography, molecular modeling, synthetic chemistry, assay specialists, parasitologists) at the University of Washington in Seattle. We believe that computational methods in the hands of a scientist who is a creative thinker and an energetic collaborator can impact all aspects of drug discovery. Project goal: development of pre-clinical drug candidates to fight neglected parasitic diseases by exploiting in-house crystal structures of tRNA-synthetases. Your responsibilities will encompass large scale molecular docking, ligand optimization by design, chemo-informatics and occasionally mass-spectrometric follow-up of metabolic studies. Qualifications: - Ph.D. degree in computational chemistry, organic chemistry or a related field. - Experience in molecular docking, chemical library design, pharmacophore techniques. - Experience with linux-based computing and proficiency in at least one programming language. - Excellent oral and written communication skills in English. - Organizational skills. Interested individuals should send an e-mail to Christophe Verlinde (verli...@u.washington.edu) containing their CV, brief summary of previous research, and contact information for three references. For more info about the lab: http://www.bmsc.washington.edu/people/verlinde/research.html Initial appointment will be for 1 year an can be extended by another year upon satisfactory performance. Start date: asap. The University of Washington is an affirmative action, equal opportunity employer.
[ccp4bb] Post-doc position available
A position is available now in the laboratory of Wim Hol, as described below. Please respond to the address at the end of the advertisement. Postdoctoral Position Available Laboratory of Wim Hol Department of Biochemistry, School of Medicine University of Washington, Seattle, USA Structural Biology of the type II secretion system from pathogenic bacteria The projects in Wim Hol’s protein crystallography group at the University of Washington are all focused on providing a basis for development of new therapeutics for tropical diseases. This particular available postdoctoral position is part of a major effort to unravel the architecture, mechanism of action and biogenesis of the “type II secretion system” (T2SS). The sophisticated T2SS occurs in many pathogenic bacteria. This machinery is responsible for translocating a wide variety of proteins in a folded state from the periplasm across the outer membrane into the extracellular milieu. One of these proteins is cholera toxin which has been studied intensively in the Hol lab. The large T2SS consists of multiple copies of ~14 different proteins that span the inner and the outer membrane, and is associated with a secretion ATPase in the cytoplasm which provides the energy for the secretion process. Another remarkable feature of the T2SS is a helical sub-assembly in the periplasm which is likely serving as a piston pushing cholera toxin and other exoproteins through a pore in the outer membrane. The successful candidate will have the opportunity to: (i) carry out protein _expression_ and protein chemistry studies to obtain insight into protein-protein interactions involving the T2SS from pathogenic bacteria like Vibrio cholera, enterotoxigenic E. coli, and other bacteria; (ii) purify and characterize multi-protein and multi-membrane protein complexes; (iii) determine high resolution crystal structures of these complexes; (iv) analyze these structures and combine this with other biochemical data; (v) interact with several collaborating groups which are using other methods to obtain structural and functional insight into the mechanism of this sophisticated secretion system. For more information regarding the laboratory of Wim Hol see the following website: http://www.bmsc.washington.edu/WimHol/ For more information regarding the type II secretion system see our recent review: Korotkov, K. V., Sandkvist, M. and Hol, W. G. J. The type II secretion system: biogenesis, molecular architecture and mechanism. Nature Reviews Microbiology 10, 336-351 (2012) START DATE: Immediately INSTITUTION: Department of Biochemistry Biomolecular Structure Center School of Medicine Box 357742 University of Washington Seattle, WA, 98195 USA Requirements Experience with membrane protein preparation, including molecular biology techniques, membrane protein characterization and protein crystallography. Application If you are interested, please send your CV, including a description of your experience and technical know-how, a list of publications and presentations, and names and email addresses of three references able to assess your scientific experience and capabilities to: wg...@u.washington.edu
[ccp4bb] Postdoctoral position available
This notice is posted on behalf of Wim Hol. Please send inquiries to him at the email address at the bottom of the page. Postdoctoral Position Available Laboratory of Wim Hol Department of Biochemistry, School of Medicine University of Washington, Seattle, USA Structural Biology of the type II secretion system from pathogenic bacteria The projects in Wim Hol’s protein crystallography group at the University of Washington are all focused on providing a basis for development of new therapeutics for tropical diseases. This particular postdoctoral position is within a collaborative project which aims to unravel the architecture, mechanism of action and biogenesis of the” type II secretion system” (T2SS). The sophisticated T2SS occurs in many pathogenic bacteria. This machinery is responsible for translocating a wide variety of proteins in a folded state from the periplasm across the outer membrane into the extracellular milieu. One of these proteins is cholera toxin which has been studied intensively in the Hol lab. The large T2SS consists of ~14 different proteins that span the inner and the outer membrane, and is associated with a secretion ATPase in the cytoplasm which provides the energy for the secretion process. Another remarkable feature of the T2SS is a helical sub-assembly in the periplasm ! which is likely serving as a piston pushing cholera toxin and other exoproteins through a pore in the outer membrane. The successful candidate will have the opportunity to: (i) carry out protein expression and protein chemistry studies to obtain insight into protein-protein interactions involving the T2SS from pathogenic bacteria like Vibrio cholera, enterotoxigenic E. coli, and other bacteria; (ii) purify and characterize multi-membrane protein complexes; (iii) determine high resolution crystal structures of multi-protein sub-complexes of the machinery; (iv) apply electron microscopy techniques in the laboratory of Dr. Tamir Gonen to enhance our insight into the architecture and functioning of the T2SS; (v) combine the results of electron microscopy and crystallography. For more information regarding the laboratory of Wim Hol see the following websites: http://www.bmsc.washington.edu/WimHol/ http://depts.washington.edu/biowww/faculty/hol.html and regarding the laboratory of Tamir Gonen: http://depts.washington.edu/biowww/faculty/gonen.html START DATE: Immediately INSTITUTION: Department of Biochemistry Biomolecular Structure Center School of Medicine Box 357742 University of Washington Seattle, WA, 98195 USA Requirements Experience with membrane protein preparation, characterization and crystallography. Application If you are interested, please send your CV, including a description of your experience and technical know-how, a list of publications and presentations, and names and email addresses of three references able to assess your scientific experience and capabilities to: wg...@u.washington.edu
[ccp4bb] Postdoctoral position available
Postdoctoral Position available in the Laboratory of Wim Hol Department of Biochemistry, School of Medicine, University of Washington, Seattle, USA Structural Biology and structure-based inhibitor design of the invasion machinery of the malaria parasite. JOB DESCRIPTION: This project aims to unravel the structure of the invasion machinery of the malaria parasite and to design inhibitors to interfere with the proper functioning of the machinery. Such inhibitors might be the foundation for new anti-malarials. The malaria parasite invades two types of cells when in the human host: hepatocytes and erythrocytes. This invasion is a fascinating and very complex process, but some features are shared in the invasion of these two different cell types. These include aldolase (yes, the glycolytic enzyme is moonlighting here...) interacting with an actin filament, a specific myosin motor interacting with the actin, a myosin-tail interacting protein (MTIP), and a number of so-called GAP proteins. We have elucidated several structures of interacting proteins in this system. There are also exciting invasion-blocking compounds which we try to co-crystallize with their target protein. The aims for the project in the next few years are; (i) to obtain additional structural information about additional proteins and multi-protein complexes of the machinery; and, (ii) to assist in structure-based design of invasion inhibitors. The project is an interdisciplinary collaboration with molecular modeling, chemical synthesis, parasitolology and biochemical groups, in the Biomolecular Structure Center of the University of Washington, Seattle, and Drexel University, Philadelphia. The successful candidate will have the opportunity to: (i) carry out protein expression and protein chemistry studies to obtain insight into protein-protein interactions involving the invasion machinery of the malaria parasite; (ii) determine high resolution crystal structures of individual proteins as well as multi-protein sub-complexes of the machinery; (iii) solve crystal structures of invasion proteins in complex with small molecule inhibitors. There will also be opportunities to carry out biophysical binding assays. Several expression systems are already available for preparing soluble proteins from the invasion machinery. For further information regarding our studies on the invasion machinery see: Bosch, J., Turley, S., Daly, T. M., Bogh, S. M., Villasimil, M. L., Roach, C., Zhou, N., Morrisey, J. M., Vaidya, A. B., Bergman, L. W. & Hol, W. G. J. (2006). Structure of the Plasmodium MTIP-MyoA complex, a key component of the malaria parasite invasion motor. Proc. Natl. Acad. Sci. USA 103, 4852-4857. Bosch, J., Buscaglia, C. A., Krumm, B. E., Ingason, B., Lucas, R., Roach, C., Cardozo, T., Nussenzweig, V. & Hol, W. G. (2007). Aldolase provides an unusual binding site for TRAP in the invasion machinery of the malaria parasite. Proc. Natl. Acad. Sci. USA, 104, 7015-8020. Bosch, J., Turley, S., Roach, C., Daly, T. M., Bergman, L. W. & Hol, W. G. (2007) The Closed MTIP-MyosinA-tail Complex from the Malaria Parasite Invasion Machinery. J Mol Biol. 372, 77-88. And for information regarding the research in our lab see the websites: http://www.bmsc.washington.edu/WimHol/ http://depts.washington.edu/biowww/faculty/hol.html JOB REQUIREMENTS: - Experience with: - protein expression and purification methods - characterization of purified soluble proteins - protein crystallization - At least three years of experience with protein structure determination methods, including: X-ray diffraction data collection and data processing; experimental and molecular replacement phasing methods; density modification; crystallographic refinement. - Excellent interpersonal skills to function optimally in the malaria invasion project team and to cooperate with collaborators in other groups and institutions. Experience in one or more of the following fields would be a plus: - Molecular biology for protein overexpression - Purification and characterization of multi-protein complexes - Biophysical binding assays - Molecular modeling for inhibitor design. START DATE: Immediately INSTITUTION:Department of Biochemistry Biomolecular Structure Center School of Medicine Box 357742 University of Washington Seattle, WA, 98195 USA Please send your CV, including a description of your experience, a list of publications, and names and email addresses of three references able to assess your scientific experience and capabilities to: wg...@u.washington.edu
[ccp4bb] Postdoctoral Fellow position
This notification is posted on behalf of Prof Wim Hol. Interested parties should reply to him at: [EMAIL PROTECTED] or at the address below. Postdoctoral Fellow Structural Biology of the RNA editing editosome JOB DESCRIPTION: The project aims at understanding the structure and functioning of the unique RNA-editing editosome from Trypanosoma brucei and related trypanosomatid protozoan species. These organisms are the causative agents of a variety of diseases in tropical and subtropical areas, including sleeping sickness in Sub-Saharan Africa, Chagas disease in Latin America and leishmaniasis throughout the tropics and subtropics. Several essential genes in the mitochondria of these protozoa undergo a fascinating U-insertion/deletion RNA editing process involving several protein and multi-protein complexes. The RNA-editing editosome of about 1.5 million Daltons performs the actual editing steps, involving an enzyme-cascade principle. The editosome consists of over 15 different proteins with most, if not all, of these proteins present in multiple copies. The goal of the project is to unravel, by molecular biology and crystallographic approaches: (i) protein-protein and protein-RNA interactions within the editosome; and, (ii) crystal structures of components and sub-complexes of this multi-protein assembly in complex with a variety of RNA molecules. Since several of the editosome proteins have been shown to be essential for the parasites, the results obtained provide a platform for structure-based drug design. The successful candidate will have the opportunity to carry out (i) molecular biology, protein expression and purification methods to obtain insight into protein-protein and protein-RNA interactions involving the editosome, and (ii) to determine high resolution crystal structures of individual editosome components, and in particular of large sub-complexes of the editosome with RNA. Numerous expression systems are already available for preparing complexes containing multiple editosome proteins. For further information regarding the editosome see: Deng, J., Schnaufer, A., Salavati, R., Stuart, K. & Hol, W. G. J. (2004). High Resolution Crystal Structure of an Editosome Enzyme from Trypanosoma brucei: RNA Editing ligase I. J Mol Biol 343, 601-613 Deng, J., Lewis Ernst, N., Turley, S., Stuart, K. & Hol, W. G. J. (2005). Structural basis for UTP specificity of RNA editing TUTases from Trypanosoma brucei. EMBO J. 24, 4007-4017. For information regarding the research in our lab see the websites: http://www.bmsc.washington.edu/WimHol/ and http://depts.washington.edu/biowww/faculty/hol.html JOB REQUIREMENTS: - Good knowledge and extensive experience with molecular biology for protein overexpression - Experience with: - protein expression and purification methods of soluble proteins in E coli - characterizing purified soluble proteins - crystallization methods for proteins - protein crystal cryo-protection procedures - protein structure determination methods, including: X-ray diffraction data collection and data processing; selenomethionine SAD and MAD phasing and/or multiple isomorphous replacement and/or molecular replacement; density modification; model building; crystallographic refinement; structure analysis and structure validation procedures using multiple computer programs and interactive graphics techniques. - Excellent interpersonal skills to function optimally in the editosome project team and to cooperate with collaborators in other institutions. The Following experience would be a plus: - Molecular biology for obtaining truncated protein variants and implementing surface mutations to enhance the probability of crystal growth - production of RNA - protein expression and purification methods of soluble proteins in insect cells START DATE: Immediately INSTITUTION:Department of Biochemistry Biomolecular Structure Center School of Medicine Box 357742 University of Washington Seattle, WA, 98195 USA
[ccp4bb] Research Scientist position available
This notice is posted at the request of Wim Hol. Interested candidates should direct their inquiries to him at the address below. Thanks Stewart RESEARCH SCIENTIST POSITION AVAILABLE Molecular Biology for Structural Studies on Proteins from Global Pathogens JOB DESCRIPTION: The projects in the protein crystallography group of Wim Hol are all focused on providing a basis for development of new therapeutics to combat tropical diseases. Current projects include molecular machines, protein-RNA complexes and integral membrane proteins. In particular the sophisticated Type 2 Protein Secretion system of cholera toxin, the unique RNA editing machinery in mitochondria of the sleeping sickness parasite, and the essential malaria parasite invasion machinery are at the center of attention. The responsibilities of the successful candidate include: (i) Design and construct plasmids and multi-plasmid systems to express and co-express protein of interest in E. coli, and in other expression systems like insect cells; (ii) Carry out site directed mutagenesis to obtain variants of the proteins under investigation with respect to length, active site characteristics, surface properties, etc.; (iii) Small scale expression of proteins and multi-protein complexes; (iv) Prepare large quantities of RNA by in vitro translation methods; (v) Maintain molecular biology, protein expression and protein purification equipment; (vi) Maintain the plasmid and expression system database of the group; Further information regarding the work of the laboratory can be found at: www.bmsc.washington.edu/WimHol depts.washington.edu/biowww/faculty/hol.html JOB REQUIREMENTS: - At least three years of experience with: - Constructing vectors with optimal properties for producing protein with various cleavable and non-cleavable affinity-chromatography purification tags. - Site-directed mutagenesis; - Over-expression of eukaryotic proteins in E. coli or other heterologous expression systems; - Management of databases containing plasmid, vector and expression information. - Maintaining molecular biology equipment. - Molecular biology software and web-based programs. - Ability to work on multiple projects simultaneously with minimal supervision. - Excellent interpersonal skills to function optimally in the project teams and to cooperate with collaborators in other institutions. - B. Sc. in biochemistry or microbiology, or equivalent. DESIRED SKILLS (not required): - Experience with production of large quantities of RNA by in vitro translation methods; and/or protein expression using baculo virus and insect cells; and/or application of phage display techniques. Interested candidates are invited to send an application plus brief CV plus names and email addresses of three references to: Wim Hol at [EMAIL PROTECTED]
