By John Vetterli [CC-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.

Description: The Tong lab at the Structural Genomics Consortium (SGC) of the University of Toronto is seeking a talented and self-motivated PhD scientist to study the structure, function and mechanism of deubiquitinases (DUBs), with a focus on the role of DUBs in stress response and gene regulation. The successful candidate will utilize the high-throughput structural biology (HTSB) platform and biochemical/biophysical techniques to study the activity and regulatory mechanisms of these enzymes.

Closing Date:
Monday 25th September 2017
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

Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors.
Torchia J, Golbourn B, Feng S, Ho KC, Sin-Chan P, Vasiljevic A, Norman JD, Guilhamon P, Garzia L, Agamez NR, Lu M, Chan TS, Picard D, de Antonellis P, Khuong-Quang DA, Planello AC, Zeller C, Barsyte-Lovejoy D, Lafay-Cousin L, Letourneau L, Bourgey M, Yu M, Gendoo DM, Dzamba M, Barszczyk M, Medina T, Riemenschneider AN, Morrissy AS, Ra YS, Ramaswamy V, Remke M, Dunham CP, Yip S, Ng HK, Lu JQ, Mehta V, Albrecht S, Pimentel J, Chan JA, Somers GR, Faria CC, Roque L, Fouladi M, Hoffman LM, Moore AS, Wang Y, Choi SA, Hansford JR, Catchpoole D, Birks DK, Foreman NK, Strother D, Klekner A, Bognár L, Garami M, Hauser P, Hortobágyi T, Wilson B, Hukin J, Carret AS, Van Meter TE, Hwang EI, Gajjar A, Chiou SH, Nakamura H, Toledano H, Fried I, Fults D, Wataya T, Fryer C, Eisenstat DD, Scheinemann K, Fleming AJ, Johnston DL, Michaud J, Zelcer S, Hammond R, Afzal S, Ramsay DA, Sirachainan N, Hongeng S, Larbcharoensub N, Grundy RG, Lulla RR, Fangusaro JR, Druker H, Bartels U, Grant R, Malkin D, McGlade CJ, Nicolaides T, Tihan T, Phillips J, Majewski J, Montpetit A, Bourque G, Bader GD, Reddy AT, Gillespie GY, Warmuth-Metz M, Rutkowski S, Tabori U, Lupien M, Brudno M, Schüller U, Pietsch T, Judkins AR, Hawkins CE, Bouffet E, Kim SK, Dirks PB, Taylor MD, Erdreich-Epstein A, Arrowsmith CH, De Carvalho DD, Rutka JT, Jabado N, Huang A
Cancer Cell. 12.12.2016 30(6):891-908. doi: 10.1016/j.ccell.2016.11.003
PMID: 27960086

Structural insights into Gemin5-guided selection of pre-snRNAs for snRNP assembly.
Xu C, Ishikawa H, Izumikawa K, Li L, He H, Nobe Y, Yamauchi Y, Shahjee HM, Wu XH, Yu YT, Isobe T, Takahashi N, Min J
Genes Dev.. 01.11.2016 30(21):2376-2390. doi: 10.1101/gad.288340.116
PMID: 27881600

Structural biology: HDAC6 finally crystal clear.
Liu Y, Li L, Min J
Nat. Chem. Biol.. 18.08.2016 12(9):660-1. doi: 10.1038/nchembio.2158
PMID: 27538024

Functional interdependence of BRD4 and DOT1L in MLL leukemia.
Gilan O, Lam EY, Becher I, Lugo D, Cannizzaro E, Joberty G, Ward A, Wiese M, Fong CY, Ftouni S, Tyler D, Stanley K, MacPherson L, Weng CF, Chan YC, Ghisi M, Smil D, Carpenter C, Brown P, Garton N, Blewitt ME, Bannister AJ, Kouzarides T, Huntly BJ, Johnstone RW, Drewes G, Dawson SJ, Arrowsmith CH, Grandi P, Prinjha RK, Dawson MA
Nat. Struct. Mol. Biol.. 13.06.2016 . doi: 10.1038/nsmb.3249
PMID: 27294782

Perspective: Science is still too closed.
Edwards A
Nature. 12.05.2016 533:S70. doi: 10.1038/533S70a
PMID: 27167397

SETD7 Controls Intestinal Regeneration and Tumorigenesis by Regulating Wnt/β-Catenin and Hippo/YAP Signaling.
Oudhoff MJ, Braam MJ, Freeman SA, Wong D, Rattray DG, Wang J, Antignano F, Snyder K, Refaeli I, Hughes MR, McNagny KM, Gold MR, Arrowsmith CH, Sato T, Rossi FM, Tatlock JH, Owen DR, Brown PJ, Zaph C
Dev. Cell. 04.04.2016 37(1):47-57. doi: 10.1016/j.devcel.2016.03.002
PMID: 27046831

Reproducibility: Team up with industry.
Edwards A
Nature. 17.03.2016 531(7594):299-301. doi: 10.1038/531299a
PMID: 26983524

System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes.
Zhang W, Wu KP, Sartori MA, Kamadurai HB, Ordureau A, Jiang C, Mercredi PY, Murchie R, Hu J, Persaud A, Mukherjee M, Li N, Doye A, Walker JR, Sheng Y, Hao Z, Li Y, Brown KR, Lemichez E, Chen J, Tong Y, Harper JW, Moffat J, Rotin D, Schulman BA, Sidhu SS
Mol. Cell. 02.03.2016 . doi: 10.1016/j.molcel.2016.02.005
PMID: 26949039

A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1.
Stuckey JI, Dickson BM, Cheng N, Liu Y, Norris JL, Cholensky SH, Tempel W, Qin S, Huber KG, Sagum C, Black K, Li F, Huang XP, Roth BL, Baughman BM, Senisterra G, Pattenden SG, Vedadi M, Brown PJ, Bedford MT, Min J, Arrowsmith CH, James LI, Frye SV
Nat. Chem. Biol.. 25.01.2016 . doi: 10.1038/nchembio.2007
PMID: 26807715

SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination.
Yanling Zhao D, Gish G, Braunschweig U, Li Y, Ni Z, Schmitges FW, Zhong G, Liu K, Li W, Moffat J, Vedadi M, Min J, Pawson TJ, Blencowe BJ, Greenblatt JF
Nature. 23.12.2015 . doi: 10.1038/nature16469
PMID: 26700805

MLL5 Orchestrates a Cancer Self-Renewal State by Repressing the Histone Variant H3.3 and Globally Reorganizing Chromatin.
Gallo M, Coutinho FJ, Vanner RJ, Gayden T, Mack SC, Murison A, Remke M, Li R, Takayama N, Desai K, Lee L, Lan X, Park NI, Barsyte-Lovejoy D, Smil D, Sturm D, Kushida MM, Head R, Cusimano MD, Bernstein M, Clarke ID, Dick JE, Pfister SM, Rich JN, Arrowsmith CH, Taylor MD, Jabado N, Bazett-Jones DP, Lupien M, Dirks PB
Cancer Cell. 25.11.2015 . doi: 10.1016/j.ccell.2015.10.005
PMID: 26626085

Chemical basis for the recognition of trimethyllysine by epigenetic reader proteins.
Kamps JJ, Huang J, Poater J, Xu C, Pieters BJ, Dong A, Min J, Sherman W, Beuming T, Matthias Bickelhaupt F, Li H, Mecinović J
Nat Commun. 19.11.2015 6:8911. doi: 10.1038/ncomms9911
PMID: 26578293

Structural basis for substrate recognition by the human N-terminal methyltransferase 1.
Dong C, Mao Y, Tempel W, Qin S, Li L, Loppnau P, Huang R, Min J
Genes Dev.. 05.11.2015 . doi: 10.1101/gad.270611.115
PMID: 26543161

STRUCTURAL BIOLOGY. Chromatin complex, crystal clear.
Schapira M
Science. 16.10.2015 350(6258):278-9. doi: 10.1126/science.aad5203
PMID: 26472895

Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth.
Zhu J, Sammons MA, Donahue G, Dou Z, Vedadi M, Getlik M, Barsyte-Lovejoy D, Al-awar R, Katona BW, Shilatifard A, Huang J, Hua X, Arrowsmith CH, Berger SL
Nature. 10.09.2015 525(7568):206-11. doi: 10.1038/nature15251
PMID: 26331536

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