About the Visiting Scientist Program
The Structural Genomics Consortium (SGC) is a not-for-profit organization that determines the three dimensional structures of proteins of medical relevance, and places them in the public domain without restriction. The SGC operates out of the Universities of Oxford and Toronto, and Karolinska Institutet, Stockholm. We work on structures of proteins from our Target List of ~2,400 proteins, which is comprised of human proteins associated with diseases such as cancer, diabetes, inflammation, and genetic diseases, as well as proteins from human parasites such as those that cause malaria. Since its inception the SGC has generated thousands of purified human and malaria-related proteins and determined over 1,000 high resolution protein structures. Published studies include: The large scale analysis of the human protein tyrosine phosphatome; The activation of apicomplexan CDPKs by calcium; Architecture of Eph receptor clusters.
As part of our mandate, the SGC has developed multiple strategies for the recombinant expression, purification, crystallization and biophysical and biochemical characterization of human and protozoan proteins. We routinely perform small molecule binding screens on our target proteins in order to identify compounds that promote protein purification or crystallization. About 20% of the SGC protein structures were determined in the presence of a compound derived from the SGC screening initiatives. Many additional complexes of SGC targets with natural and synthetic ligands were determined to gain insight into the mechanism of protein/ligand protein/peptide and protein-protein interactions. Examples include studies on recognition of hemi-methylated DNA by UHRF1; SH2-kinase domain interactions in Fes and Abl; the structural basis for inhibitor specificity in human PARP3; histone demethylase JMJD2A substrate specificity; Structural studies of the PLAA/Ufd3-p97/Cdc48 complex.
The SGC has also recently initiated two multinational studies aimed at developing "open access" reagents for epigenetics research. One project involves the production of chemical probes that are optimized for potency, epigenetic target selectivity and cellular activity. The second project involves the production of recombinant, renewable affinity reagents to human proteins, including epigenetic targets and SH2 domain proteins, which will be made available to the research community.
The SGC welcomes collaborations with the biomedical research community on proteins of mutual interest. The SGC organizes its research around protein families of related biochemical function and of therapeutic interest. Collaborative opportunities exist for visiting scientists, graduate students and postdoctoral fellows to work for 6-12 month terms at an SGC site on SGC targets of mutual interest. Guest scientists are expected to cover their own salary and local accommodations, and the SGC will pay for laboratory supplies and equipment. Guest Scientists would be expected to work on SGC target proteins with the goal of obtaining a 3D structure or of developing open access reagents. Examples of joint publications by visiting scientists and SGC scientists include:
- Thermolability of mutant MMACHC protein in the vitamin B12-responsive cblC disorder
- Crystal structure of the human ubiquitin-activating enzyme 5 (UBA5) bound to ATP: Mechanistic insights into a minimalistic E1 enzyme.
- Structure and function of the intracellular region of the plexin-b1 transmembrane receptor.
- Dynamic protein methylation in chromatin biology.
- Distinguishing between calpain heterodimerization and homodimerization.
Examples of potential projects include:
- Expression and purification of active, recombinant proteins or complexes
- Crystallization and structure determination of proteins
- Functional (biochemical) characterization of proteins including enzyme assays, protein-protein or protein-small molecule interactions combined with structure determination of proteins and/or complexes.
- Structure determination and biophysical characterization of proteins including stability and activities of SNP variants
- Identification of chemical probes to epigenetic targets
- Development of recombinant antibodies/clamps against SGC target proteins
This is an excellent training opportunity for young scientists in high throughput protein expression, structural biology, and biophysical characterization techniques.
Interested applicants are encouraged to download the Application Form and outline their project proposal.
To submit the application or for further information, please contact:
susanneSusanne Muller-Knappmuller-knappsgcsgcsgcoxacukuksusannemk1Hidden_required_JavaScript_turn_on
Structural Genomics Consortium (SGC Oxford)
University of Oxford
Old Road Campus Research Building
Roosevelt Drive
Headington, Oxford, OX3 7DQ
UK
