jin rongsheng uc irvine factory

Structure and function of bacterial toxins and receptors; synaptic proteins; protein complexes; protein-protein and protein-ligand interactions; X-ray crystallography; high-throughput screening

Our research group is dedicated to understand the molecular basis of human diseases using structural biology, which allows us to visualize how proteins function or malfunction at the atomic level. Our current research is focused on three areas: (1) exploring the molecular mechanisms underlying the toxic and therapeutic functions of botulinum neurotoxins (BoNTs), which will help to develop effective anti-BoNT strategies and improve clinical applications of BoNT; (2) characterizing the structures of Clostridium difficile (C. diff) toxins (TcdA and TcdB) and their interactions with host receptors, and understanding how they contribute to the disease of Clostridium difficile infection (CDI) that tops the CDC’s list of urgent threats; (3) advancing mechanistic understanding of ion channels, receptors, and signaling molecules in the nervous system, which will facilitate the design and improvement of therapeutic agents for the treatment of some psychological and neurological disorders. We are also developing cutting-edge small molecule high-throughput screening (HTS) assays based on our understanding of the structure and function of these disease-related proteins, which may lead to novel chemical probes and/or drug candidates for basic research and therapeutic application.

Lam, K. H., Guo, Z., Krez, N., Matsui, T., Perry, K., Weisemann, J., Rummel, A., Bowen, M. E. & Jin, R. A viral-fusion-peptide-like molecular switch drives membrane insertion of botulinum neurotoxin A1. Nat Commun 9, 5367 (2018) doi: 10.1038/s41467-018-07789-4.

Chen, P., Tao, L., Liu, Z., Dong, M. & Jin, R. Structural insight into Wnt signaling inhibition by Clostridium difficile toxin B. FEBS J (2018) doi: 10.1111/febs.14681.

Chen, P., Tao, L., Wang, T., Zhang, J., He, A., Lam, K. H., Liu, Z., He, X., Perry, K., Dong, M*. & Jin, R*. Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B. Science 360, 664-669 (2018) (*corresponding authors) doi: 10.1126/science.aar1999. PMCID: PMC6231499

Lam, K. H., Sikorra, S., Weisemann, J., Maatsch, H., Perry, K., Rummel, A., Binz, T. & Jin, R. Structural and biochemical characterization of the protease domain of the mosaic botulinum neurotoxin type HA. Pathog Dis 76 (2018) doi: 10.1093/femspd/fty044. PMCID: PMC5961070

Silva, D. A., Stewart, L., Lam, K. H., Jin, R. & Baker, D. Structures and disulfide cross-linking of de novo designed therapeutic mini-proteins. FEBS J 285, 1783-1785 (2018) doi: 10.1111/febs.14394. PMCID: PMC6001749

Lam, K. H., Qi, R., Liu, S., Kroh, A., Yao, G., Perry, K., Rummel, A. & Jin, R. The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein. Toxicon 147, 19-26 (2018) doi: 10.1016/j.toxicon.2017.10.012. PMCID: PMC5902665

Chevalier, A., Silva, D.A., Rocklin, G.J., Hicks, D.R., Vergara, R., Murapa, P., Bernard, S.M., Zhang, L., Lam, K.H., Yao, G., Bahl, C.D., Miyashita, S.I., Goreshnik, I., Fuller, J.T., Koday, M.T., Jenkins, C.M., Colvin, T., Carter, L., Bohn, A., Bryan, C.M., Fernández-Velasco, D.A., Stewart, L., Dong, M., Huang, X., Jin, R., Wilson, I.A., Fuller, D.H. & Baker, D. Massively parallel de novo protein design for targeted therapeutics. Nature 550(7674):74-79 (2017) doi: 10.1038/nature23912. PMCID: PMC5802399

Yao, G., Lam, K.H., Weisemann, J., Peng, L., Krez, N., Perry, K., Shoemaker, C.B., Dong, M., Rummel, A. & Jin, R. A camelid single-domain antibody neutralizes botulinum neurotoxin A by blocking host receptor binding. Sci Rep. 7;7(1):7438. (2017) doi: 10.1038/s41598-017-07457-5. PMCID: PMC5547058

Yao, G., Lam, K.H., Perry, K., Weisemann, J., Rummel, A. & Jin, R. Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H. Toxins (Basel) 9, 93 (2017) doi: 10.3390/toxins9030093. PMCID: PMC5371848

Yao, G., Zhang, S., Mahrhold, S., Lam, K. H., Stern, D., Bagramyan, K., Perry, K., Kalkum, M., Rummel, A.*, Dong, M.* & Jin, R.* N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A. Nat Struct Mol Biol 23 (7):656-662 (2016) (*corresponding authors) doi: 10.1038/nsmb.3245. PMCID: PMC5033645

Lee, K., Lam, K. H., Kruel, A. M., Mahrhold, S., Perry, K., Cheng, L. W., Rummel, A. & Jin, R. Inhibiting oral intoxication of botulinum neurotoxin A complex by carbohydrate receptor mimics. Toxicon 107, 43-49 (2015) doi: 10.1016/j.toxicon.2015.08.003. PMCID: PMC4658216

Lam, K.H. & Jin, R. Architecture of the botulinum neurotoxin complex: a molecular machine for protection and delivery. Current Opinion in Structural Biology 31:89-95 (2015) doi: 10.1016/j.sbi.2015.03.013. PMCID: PMC4476938

Lam, K.H., Yao, G. & Jin, R. Diverse binding modes, same goal: The receptor recognition mechanism of botulinum neurotoxin. Progress in Biophysics and Molecular Biology 117(2-3):225-31 (2015) doi: 10.1016/j.pbiomolbio.2015.02.004. PMCID: PMC4417461

Lam, T.I., Stanker, L.H., Lee, K., Jin, R. & Cheng, L.W. Translocation of botulinum neurotoxin serotype A and associated proteins across the intestinal epithelia. Cellular Microbiology 17(8):1133-1143 (2015) doi: 10.1111/cmi.12424. PMCID: PMC4610714

Matsui, T.*, Gu, S., Lam, K.H., Carter, L.G., Rummel, A., Mathews, II. & Jin, R.* Structural Basis of the pH-Dependent Assembly of a Botulinum Neurotoxin Complex. J. Mol. Biol. 426(22):3773-3782 (2014) doi: 10.1016/j.jmb.2014.09.009. (*corresponding authors) PMCID: PMC4252799

Lee, K., Zhong, X., Gu, S., Kruel, A.M., Dorner, M.B., Perry, K., Rummel, A., Dong, M. & Jin, R. Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex. Science 344(6190):1405-1410 (2014) doi: 10.1126/science.1253823. PMCID: PMC4164303

Lee, K., Lam, K.H., Kruel, A.M., Perry, K., Rummel, A. and Jin, R. High-resolution crystal structure of HA33 of botulinum neurotoxin type B progenitor toxin complex. Biochem. Biophys. Res. Commun. 446(2):568-573 (2014) doi: 10.1016/j.bbrc.2014.03.008. PMCID: PMC4020412

Yao, Y., Lee, K., Gu, S., Lam, K.H. & Jin, R. Botulinum Neurotoxin A Complex Recognizes Host Carbohydrates through Its Hemagglutinin Component, Toxins (Basel) 6(2):624-635 (2014) doi: 10.3390/toxins6020624. PMCID: PMC3942755

Lee, K., Gu, S., Jin, L., Le, T.T.N., Cheng, L.W., Strotmeier, J., Kruel, A.M., Yao, G., Perry, K., Rummel, A.* & Jin, R.* Structure of a Bimodular Botulinum Neurotoxin Complex Provides Insights into Its Oral Toxicity. PLoS Pathog. 9(10): e1003690 (2013) doi:10.1371/journal.ppat.1003690. (*corresponding authors) PMCID: PMC3795040

Zong, Y. and Jin, R. Structural mechanisms of the agrin-LRP4-MuSK signaling pathway in neuromuscular junction differentiation. Cell. Mol. Life Sci. 70(17):3077-88 (2013) doi: 10.1007/s00018-012-1209-9. PMCID: PMC4627850

Gu, S. and Jin, R. Assembly and function of the botulinum neurotoxin progenitor complex. Curr. Top. Microbiol. Immunol. 364:21-44 (2013) doi: 10.1007/978-3-642-33570-9_2. PMCID: PMC3875173

Gu, S., Rumpel, S., Zhou, J., Strotmeier, J., Bigalke, H., Perry, K., Shoemaker, C.B., Rummel, A. & Jin, R. Botulinum neurotoxin is shielded by NTNHA in an interlocked complex. Science 335(6071):977-81 (2012) doi: 10.1126/science.1214270. PMCID: PMC3545708

Zong, Y., Zhang, B., Gu, S., Lee, K., Zhou, J., Yao, G., Figueiredo, D., Perry, K., Mei, L.* & Jin, R.* Structural basis of neuron-specific regulation of postsynaptic differentiation. Gene & Development 26:247-258 (2012) doi: 10.1101/gad.180885.111. (*corresponding authors) PMCID: PMC3278892

Yao, G., Zong, Y., Gu, S., Zhou, J., Xu, H., Mathews, II. & Jin, R. Crystal structure of the glutamate receptor GluA1 amino-terminal domain. Biochem. J. 438(2):255-63 (2011) doi: 10.1042/BJ20110801. PMCID: PMC3296483

Strotmeier, J., Gu, S., Jutzi, S., Mahrhold, S., Zhou, J., Pich, A., Eichner, T., Bigalke, H., Rummel, A.*, Jin, R.* & Binz, T*. The biological activity of botulinum neurotoxin type C is dependent upon novel types of ganglioside binding sites. Mol. Microbiol. 81(1):143-56 (2011) doi: 10.1111/j.1365-2958.2011.07682.x. Epub 2011 Jun 2. (*corresponding authors)

Strotmeier, J., Lee, K., Völker, A.K., Mahrhold, S., Zong, Y., Zeiser, J., Zhou, J., Pich, A., Bigalke, H., Binz, T., Rummel, A.* & Jin, R.* Botulinum neurotoxin serotype D attacks neurons via two carbohydrate-binding sites in a ganglioside-dependent manner. Biochem. J. 431(2):207-16 (2010) (*corresponding authors)

Jin, R.*, Singh, S.K., Gu, S., Furukawa, H., Sobolevsky, A.I., Zhou, J., Jin, Y. & Gouaux E.* Crystal structure and association behavior of the GluR2 amino-terminal domain. EMBO J. 28(12):1812-23 (2009) (*corresponding authors) PMCID: PMC2699365

Kumar, J., Schuck. P., Jin, R. & Mayer, M.L. The N-terminal domain of GluR6-subtype glutamate receptor ion channels. Nat. Struct. Mol. Biol. 16(6):631-8 (2009) PMCID: PMC2729365

Jin, R., Rummel, A., Binz, T. & Brunger, A.T. Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity. Nature 444:1092-5 (2006)

Jin, R., Clark, S., Weeks, A.M., Dudman, J.T., Gouaux, E. & Partin, K.M. Mechanism of positive allosteric modulators acting on AMPA receptors. J. Neurosci. 25(39):9027-36 (2005)

Jin, R., Junutula, J.R., Matern, H.T., Ervin, K.E., Scheller, R.H. & Brunger, A.T. Exo84 and Sec5 are competitive regulatory Sec6/8 effectors to the RalA GTPase. EMBO J. 24:2064-74 (2005)

Jin, R., Bank, T., Mayer, M. L., Traynelis, S. & Gouaux, E. Structural basis for partial agonist action at ionotropic glutamate receptors. Nat. Neurosci. 6(8):803-10 (2003)

Structure of the glucosyltransferase domain of TcdA in complex with RhoA provides insights into substrate recognition. Sci Rep. 2022 05 30; 12(1):9028.

Jahid S, Ortega JA, Vuong LM, Acquistapace IM, Hachey SJ, Flesher JL, La Serra MA, Brindani N, La Sala G, Manigrasso J, Arencibia JM, Bertozzi SM, Summa M, Bertorelli R, Armirotti A, Jin R, Liu Z, Chen CF, Edwards R, Hughes CCW, De Vivo M, Ganesan AK. PMID: 35385746; PMCID: PMC9127750.

Probing the structure and function of the protease domain of botulinum neurotoxins using single-domain antibodies. PLoS Pathog. 2022 01; 18(1):e1010169.

Chen P, Zeng J, Liu Z, Thaker H, Wang S, Tian S, Zhang J, Tao L, Gutierrez CB, Xing L, Gerhard R, Huang L, Dong M, Jin R. PMID: 34145250; PMCID: PMC8213806.

Structural Insights into Rational Design of Single-Domain Antibody-Based Antitoxins against Botulinum Neurotoxins. Cell Rep. 2020 02 25; 30(8):2526-2539.e6.

Chen P, Lam KH, Liu Z, Mindlin FA, Chen B, Gutierrez CB, Huang L, Zhang Y, Hamza T, Feng H, Matsui T, Bowen ME, Perry K, Jin R. PMID: 31308519; PMCID: PMC6684407.

The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein. Toxicon. 2018 Jun 01; 147:19-26.

High-resolution crystal structure of HA33 of botulinum neurotoxin type B progenitor toxin complex. Biochem Biophys Res Commun. 2014 Apr 04; 446(2):568-73.

The Division of Finance and Administration (DFA) provides services and support to over 50,000 students, faculty, and staff with the mission of advancing UCI’s brilliant future and the vision of becoming world-class campus partners. DFA serves the university as planning partners, problem solvers, and solution providers—striving to make it as easy as possible for people to get the services they need, when they need them. Facilities Management is proud to support the campus mission of advancing UCI"s brilliant future by creating a physical environment that allows our students, faculty and staff to thrive. Our goal is to provide safe, reliable and clean spaces through high quality maintenance, operation, planning and renovation services for our 1,475-acre main campus. We accomplish this with our dedicated skilled staff who strive to provide excellent customer service and responsiveness.

Plant Operations and Maintenance has primary responsibility for the operation, maintenance, service, and repair of Central Plant, building, machinery and utility systems at UCI. Responsibility for, but not limited to, the operation, maintenance, and cleaning of the combustion turbine generator; steam turbine generator; heat recovery system; AQMD emissions reduction systems; gas compressor; related electrical equipment and systems; high pressure, multi-fuel and HTHW boilers; both steam and electric chillers; cooling tower; air compressors; water softeners; high temperature hot water generators; air dryer systems; vacuum systems; emergency generators; all auxiliary equipment and any other equipment under the jurisdiction of the Central Plant. Maintain accurate records of equipment operation and maintenance on log sheets and logbooks. Maintain accurate records of time and materials used for equipment repairs and maintenance. Provide emergency services, excellent customer communications and services to the campus community. The position is responsible for assisting in the development, implementation and maintenance of a preventive and corrective maintenance program to insure reliable operation of the central plant and an accurate maintenance history of all plant and building equipment. The position will also perform operational, maintenance and other duties as assigned, associated with the central plant.

Must have oral and written communication skills adequate to convey instructions, directions and information to co-workers, managers, customers, and contractors.

Must be familiar with and comply with specific and detailed safety procedures, such as biosafety and confined entry requirements, radiation safety and biosafety protocols, asbestos removal procedures, specifics of Material Safety Data Sheets, etc Must be able to appropriately wear personal protective equipment (PPE) such as masks, goggles, face shields, gowns, gloves and protective safety equipment such as safety glasses and safety shoes. Must possess a valid California Driver’s License and participate in the DMV Pull program.

Must be able to work scheduled/unscheduled overtime, during weekends, holidays, and off-shift periods and be accessible by telephone Must have the physical stamina to work in inclement weather (hot/cold) conditions, confined spaces, from ladders, scaffolds, roofs, etc. Must be able to climb a vertical ladder to the height of approximately 50 feet. This position does not permit smoking anywhere on UCI campus. Must be compliant with UC Vaccination Policy .

Final candidate subject to background check. As a federal contractor, UC Irvine is required to use E-Verify to confirm the work status of individuals assigned to perform substantial work under certain federal contracts/subcontracts.

The University of California, Irvine is an Equal Opportunity/Affirmative Action Employer advancing inclusive excellence. All qualified applicants will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability, age, protected veteran status, or other protected categories covered by the UC nondiscrimination policy.

UCI provides reasonable accommodations for applicants with disabilities upon request. For more information, please contact Human Resources at (949) 824-0500.

Kitchell led the design-build delivery of two central plants to increase capacity for UC Irvine Medical Center. This project includes a new chiller plant and emergency power yard that consolidates utilities for all non-HCAI (formerly OSHPD) buildings on campus. The plant accommodates four (two installed) water-cooled chillers and two (one installed) 2,000-ton cooling towers at ultimate capacity. The design and construction of the plant considers the additional chillers, cooling tower and auxiliary equipment for future installation and can be installed in place without major modifications or disruptions. The building also obtained LEED Silver certification and addressed environmental responses to water and energy consumption with solutions like bio-retention planters.

The project’s goals were practical — consolidate utilities; reduce campus energy usage; reduce maintenance costs; and provide redundancy. However, the design-build team proved practical can also be beautiful. While addressing the heavy pedestrian traffic for construction, the team recognized the building could be a positive influence to provide visibility into the plant and educate pedestrians about the functionality of the various components and equipment of the central plant. They presented UCI with a solution that put “Science on Display.” The result? A visually stunning building. Unlike typical central plants that are purposefully hidden, the new central plant acts as a gateway marker to the campus entry by day and lends dramatic lighting in the evening.