By John Vetterli [CC-BY-SA-2.0 (http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

The SGC Toronto scientists seek to determine the 3D structures of human proteins of therapeutic relevance to diseases such as cancer and metabolic disorders. We have a particular focus on proteins involved in intracellular small molecule metabolism, enzymes involved in the transfer of methyl, acetyl and Ubiquitin-like groups, proteases and nucleotide triphosphatases. We are also investigating proteins from Plasmodium falciparum (and its apicomplexan relatives) which causes malaria.

The SGC Toronto laboratories, under the direction of Prof. Cheryl Arrowsmith, are housed within the Faculty of Medicine at the University of Toronto and located in the MaRS Discovery District, at the heart of cosmopolitan Toronto. Scientists at SGC Toronto are affiliated with several University Departments including the Banting and Best Department of Medical Research, the Departments of Physiology, Pharmacology, Medical Biophysics, and Medical Genetics and Microbiology.

The SGC Toronto laboratories have research efforts in biotechnology, laboratory automation, protein expression, protein crystallization and X-ray crystallography.

The SGC encourages collaborations with laboratories from across the globe on proteins that are currently on our target list. In addition, scientists from Ontario can nominate protein targets of pharmaceutical or biomedical relevance via the Ontario Genomics Institute. Nominated targets should be human proteins or proteins from human parasites for which a 3D protein structure will aid biomedical research. Download target nomination form here.


Watch this brief video highlighting the SGC and its innovative work at the University of Toronto.

There are currently no open vacancies with the SGC Toronto. Please check back periodically for opportunities which may arise in any of our sites.

 

Identification of a cellularly active SIRT6 allosteric activator.
Huang Z, Zhao J, Deng W, Chen Y, Shang J, Song K, Zhang L, Wang C, Lu S, Yang X, He B, Min J, Hu H, Tan M, Xu J, Zhang Q, Zhong J, Sun X, Mao Z, Lin H, Xiao M, Chin YE, Jiang H, Xu Y, Chen G, Zhang J
Nat. Chem. Biol.. 29.10.2018 . doi: 10.1038/s41589-018-0150-0
PMID: 30374165

MYC Interacts with the G9a Histone Methyltransferase to Drive Transcriptional Repression and Tumorigenesis.
Tu WB, Shiah YJ, Lourenco C, Mullen PJ, Dingar D, Redel C, Tamachi A, Ba-Alawi W, Aman A, Al-Awar R, Cescon DW, Haibe-Kains B, Arrowsmith CH, Raught B, Boutros PC, Penn LZ
Cancer Cell. 08.10.2018 34(4):579-595.e8. doi: 10.1016/j.ccell.2018.09.001
PMID: 30300580

The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates.
Jakobsson ME, Małecki JM, Halabelian L, Nilges BS, Pinto R, Kudithipudi S, Munk S, Davydova E, Zuhairi FR, Arrowsmith CH, Jeltsch A, Leidel SA, Olsen JV, Falnes PØ
Nat Commun. 24.08.2018 9(1):3411. doi: 10.1038/s41467-018-05646-y
PMID: 30143613

Architecture of the native major royal jelly protein 1 oligomer.
Tian W, Li M, Guo H, Peng W, Xue X, Hu Y, Liu Y, Zhao Y, Fang X, Wang K, Li X, Tong Y, Conlon MA, Wu W, Ren F, Chen Z
Nat Commun. 22.08.2018 9(1):3373. doi: 10.1038/s41467-018-05619-1
PMID: 30135511

DOT1L inhibition attenuates graft-versus-host disease by allogeneic T cells in adoptive immunotherapy models.
Kagoya Y, Nakatsugawa M, Saso K, Guo T, Anczurowski M, Wang CH, Butler MO, Arrowsmith CH, Hirano N
Nat Commun. 15.05.2018 9(1):1915. doi: 10.1038/s41467-018-04262-0
PMID: 29765028

Molecular basis of GID4-mediated recognition of degrons for the Pro/N-end rule pathway.
Dong C, Zhang H, Li L, Tempel W, Loppnau P, Min J
Nat. Chem. Biol.. 09.04.2018 . doi: 10.1038/s41589-018-0036-1
PMID: 29632410

Structural and functional analysis of the DOT1L-AF10 complex reveals mechanistic insights into MLL-AF10-associated leukemogenesis.
Zhang H, Zhou B, Qin S, Xu J, Harding R, Tempel W, Nayak V, Li Y, Loppnau P, Dou Y, Min J
Genes Dev.. 21.03.2018 . doi: 10.1101/gad.311639.118
PMID: 29563185

H3K14ac is linked to methylation of H3K9 by the triple Tudor domain of SETDB1.
Jurkowska RZ, Qin S, Kungulovski G, Tempel W, Liu Y, Bashtrykov P, Stiefelmaier J, Jurkowski TP, Kudithipudi S, Weirich S, Tamas R, Wu H, Dombrovski L, Loppnau P, Reinhardt R, Min J, Jeltsch A
Nat Commun. 12.12.2017 8(1):2057. doi: 10.1038/s41467-017-02259-9
PMID: 29234025

Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors.
Dahlin JL, Nelson KM, Strasser JM, Barsyte-Lovejoy D, Szewczyk MM, Organ S, Cuellar M, Singh G, Shrimp JH, Nguyen N, Meier JL, Arrowsmith CH, Brown PJ, Baell JB, Walters MA
Nat Commun. 15.11.2017 8(1):1527. doi: 10.1038/s41467-017-01657-3
PMID: 29142305

Structural basis for arginine methylation-independent recognition of PIWIL1 by TDRD2.
Zhang H, Liu K, Izumi N, Huang H, Ding D, Ni Z, Sidhu SS, Chen C, Tomari Y, Min J
Proc. Natl. Acad. Sci. U.S.A.. 08.11.2017 . doi: 10.1073/pnas.1711486114
PMID: 29118143

WD40 repeat domain proteins: a novel target class?
Schapira M, Tyers M, Torrent M, Arrowsmith CH
Nat Rev Drug Discov. 13.10.2017 . doi: 10.1038/nrd.2017.179
PMID: 29026209

A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer.
Mello SS, Valente LJ, Raj N, Seoane JA, Flowers BM, McClendon J, Bieging-Rolett KT, Lee J, Ivanochko D, Kozak MM, Chang DT, Longacre TA, Koong AC, Arrowsmith CH, Kim SK, Vogel H, Wood LD, Hruban RH, Curtis C, Attardi LD
Cancer Cell. 09.10.2017 32(4):460-473.e6. doi: 10.1016/j.ccell.2017.09.007
PMID: 29017057

A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission.
Baker DA, Stewart LB, Large JM, Bowyer PW, Ansell KH, Jiménez-Díaz MB, El Bakkouri M, Birchall K, Dechering KJ, Bouloc NS, Coombs PJ, Whalley D, Harding DJ, Smiljanic-Hurley E, Wheldon MC, Walker EM, Dessens JT, Lafuente MJ, Sanz LM, Gamo FJ, Ferrer SB, Hui R, Bousema T, Angulo-Barturén I, Merritt AT, Croft SL, Gutteridge WE, Kettleborough CA, Osborne SA
Nat Commun. 05.09.2017 8(1):430. doi: 10.1038/s41467-017-00572-x
PMID: 28874661

First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor.
Moody JD, Levy S, Mathieu J, Xing Y, Kim W, Dong C, Tempel W, Robitaille AM, Dang LT, Ferreccio A, Detraux D, Sidhu S, Zhu L, Carter L, Xu C, Valensisi C, Wang Y, Hawkins RD, Min J, Moon RT, Orkin SH, Baker D, Ruohola-Baker H
Proc. Natl. Acad. Sci. U.S.A.. 01.09.2017 . doi: 10.1073/pnas.1706907114
PMID: 28864533

Role of remodeling and spacing factor 1 in histone H2A ubiquitination-mediated gene silencing.
Zhang Z, Jones AE, Wu W, Kim J, Kang Y, Bi X, Gu Y, Popov IK, Renfrow MB, Vassylyeva MN, Vassylyev DG, Giles KE, Chen D, Kumar A, Fan Y, Tong Y, Liu CF, An W, Chang C, Luo J, Chow LT, Wang H
Proc. Natl. Acad. Sci. U.S.A.. 30.08.2017 . doi: 10.1073/pnas.1711158114
PMID: 28855339

TFG facilitates outer coat disassembly on COPII transport carriers to promote tethering and fusion with ER-Golgi intermediate compartments.
Hanna MG, Block S, Frankel EB, Hou F, Johnson A, Yuan L, Knight G, Moresco JJ, Yates JR, Ashton R, Schekman R, Tong Y, Audhya A
Proc. Natl. Acad. Sci. U.S.A.. 29.08.2017 . doi: 10.1073/pnas.1709120114
PMID: 28851831

Global analysis of protein folding using massively parallel design, synthesis, and testing.
Rocklin GJ, Chidyausiku TM, Goreshnik I, Ford A, Houliston S, Lemak A, Carter L, Ravichandran R, Mulligan VK, Chevalier A, Arrowsmith CH, Baker D
Science. 14.07.2017 357(6347):168-175. doi: 10.1126/science.aan0693
PMID: 28706065

The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex.
He Y, Selvaraju S, Curtin ML, Jakob CG, Zhu H, Comess KM, Shaw B, The J, Lima-Fernandes E, Szewczyk MM, Cheng D, Klinge KL, Li HQ, Pliushchev M, Algire MA, Maag D, Guo J, Dietrich J, Panchal SC, Petros AM, Sweis RF, Torrent M, Bigelow LJ, Senisterra G, Li F, Kennedy S, Wu Q, Osterling DJ, Lindley DJ, Gao W, Galasinski S, Barsyte-Lovejoy D, Vedadi M, Buchanan FG, Arrowsmith CH, Chiang GG, Sun C, Pappano WN
Nat. Chem. Biol.. 30.01.2017 . doi: 10.1038/nchembio.2306
PMID: 28135237

The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity.
Bromberg KD, Mitchell TR, Upadhyay AK, Jakob CG, Jhala MA, Comess KM, Lasko LM, Li C, Tuzon CT, Dai Y, Li F, Eram MS, Nuber A, Soni NB, Manaves V, Algire MA, Sweis RF, Torrent M, Schotta G, Sun C, Michaelides MR, Shoemaker AR, Arrowsmith CH, Brown PJ, Santhakumar V, Martin A, Rice JC, Chiang GG, Vedadi M, Barsyte-Lovejoy D, Pappano WN
Nat. Chem. Biol.. 23.01.2017 . doi: 10.1038/nchembio.2282
PMID: 28114273

Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma.
Veschi V, Liu Z, Voss TC, Ozbun L, Gryder B, Yan C, Hu Y, Ma A, Jin J, Mazur SJ, Lam N, Souza BK, Giannini G, Hager GL, Arrowsmith CH, Khan J, Appella E, Thiele CJ
Cancer Cell. 09.01.2017 31(1):50-63. doi: 10.1016/j.ccell.2016.12.002
PMID: 28073004

glqxz9283 sfy39587stf02 mnesdcuix8
sfy39587stf03