The Joint Center for Structural Genomics (JCSG) aims to participate in the NIGMS PSI:Biology program as a Center for High-Throughput Structure Determination. The JCSG high-throughput (HT) platform assembled over the past ten years will efficiently deliver large numbers of protein structures to the community by both x-ray crystallography and NMR on a wide range of targets from bacteria to human, including challenging targets such as eukaryotic proteins, protein-protein and other macromolecular complexes. Throughout PSI:Biology, the JCSG will adapt and tailor its operations to achieve the programmatic goals as they grow and evolve. The JCSG will continue to develop new technologies and methodologies, both experimental and computational, to address the spectrum of targets that will be presented, while keeping cost per structure to a minimum and quality to the highest standard. Integration within the PSI Network will be a high priority to embrace interactions with the Biology Partnership centers, future PARS, and the community, as well as support for all PSI Network activities, including the PSI-SGKB and PSI-MR. The JCSG will capitalize on its extensive experience to develop the best strategies to enhance chances of success and eliminate those that lead to failure. Contribution to the original PSI mission of extending structural coverage of the expanding protein universe will be advanced through judicious choice of targets, as will development of tools and collaborations that facilitate dissection of entire networks, pathways and molecular machineries for single organisms or cells from a structural perspective. The biomedical theme project will focus on the human microbiome. Interactions of commensal bacteria with the human body are profound and have a significant impact on maintenance of general human health, but are also associated with obesity, inflammatory diseases, diabetes and certain cancers to name but a few. The JCSG will leverage its HT platform to promote the biological and biomedical impact of all of its structures through extensive biophysical, functional and bioinformatics analyses in collaboration with the other PSI:Biology participants. Thus, the overall goal is to provide a robust, flexible HT structure determination platform that will meet the challenges and embrace the new opportunities that arise from the projects emanating from the PSI:Biology Partnerships and other PSI-supported projects. Furthermore, we will strive along with the PSI Network to promote widespread use of the PSI resources, materials, methodologies, data and models to the general scientific community.

Public Health Relevance

Many of the targets have direct relevance to human disease. Commensal bacteria in the human gut provide tremendous metabolic benefits, but perturbation of the symbiotic balance is linked to obesity, cancer, and inflammatory and other diseases. Structural and biological studies of proteins from the human microbiome (gut and other) and other biomedically important PSI:Biology targets will provide invaluable insights into their function and enhance discovery of new therapeutics and treatments for disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54GM094586-04
Application #
8511710
Study Section
Special Emphasis Panel (ZGM1-CBB-4 (HT))
Program Officer
Edmonds, Charles G
Project Start
2010-09-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$7,920,067
Indirect Cost
$1,709,107
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Roncase, Emily J; Moon, Clara; Chatterjee, Sandip et al. (2017) Substrate Profiling and High Resolution Co-complex Crystal Structure of a Secreted C11 Protease Conserved across Commensal Bacteria. ACS Chem Biol 12:1556-1565
Guenaga, Javier; Garces, Fernando; de Val, Natalia et al. (2017) Glycine Substitution at Helix-to-Coil Transitions Facilitates the Structural Determination of a Stabilized Subtype C HIV Envelope Glycoprotein. Immunity 46:792-803.e3
Tzarum, Netanel; McBride, Ryan; Nycholat, Corwin M et al. (2017) Unique Structural Features of Influenza Virus H15 Hemagglutinin. J Virol 91:
Gopal, Radhika; Jackson, Kelli; Tzarum, Netanel et al. (2017) Probing the antigenicity of hepatitis C virus envelope glycoprotein complex by high-throughput mutagenesis. PLoS Pathog 13:e1006735
Tzarum, Netanel; de Vries, Robert P; Peng, Wenjie et al. (2017) The 150-Loop Restricts the Host Specificity of Human H10N8 Influenza Virus. Cell Rep 19:235-245
McLuskey, Karen; Grewal, Jaspreet S; Das, Debanu et al. (2016) Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome. J Biol Chem 291:9482-91
Kong, Leopold; Lee, David E; Kadam, Rameshwar U et al. (2016) Structural flexibility at a major conserved antibody target on hepatitis C virus E2 antigen. Proc Natl Acad Sci U S A :
Xu, Qingping; Shoji, Mikio; Shibata, Satoshi et al. (2016) A Distinct Type of Pilus from the Human Microbiome. Cell 165:690-703
Serrano, Pedro; Dutta, Samit K; Proudfoot, Andrew et al. (2016) NMR in structural genomics to increase structural coverage of the protein universe: Delivered by Prof. Kurt W├╝thrich on 7 July 2013 at the 38th FEBS Congress in St. Petersburg, Russia. FEBS J 283:3870-3881
Proudfoot, Andrew; Geralt, Michael; Elsliger, Marc-Andre et al. (2016) Dynamic Local Polymorphisms in the Gbx1 Homeodomain Induced by DNA Binding. Structure 24:1372-1379

Showing the most recent 10 out of 128 publications