Susanne Gräslund

Principal Investigator

University of Toronto

Susanne Gräslund did her doctoral training in Biotechnology at the Royal Institute of Technology in Stockholm, Sweden. After her dissertation in 2002 she worked for three years at Biovitrum AB in the Target Expression & Purification section. In March 2005, Susanne joined the newly started Structural Genomics Consortium group in Stockholm as head of the Biotechnology team. She was then recruited to the SGC Toronto site as Principal Investigator for the Biotechnology team in September 2011.

Research Areas

The Biotechnology team is responsible for running a high-throughput generic protein production process and constantly improving the core methodology used at SGC to produce high-quality proteins. The group performs high-throughput cloning into a range of vectors for expression in different hosts and with different tags. Small-scale expression screening is used to identify promising candidates for scale-up production. Large-scale cultivation of bacteria is performed in LEX systems whereas shake flasks or the Wave Bioreactor are used for insect or mammalian cells. The generic protein purification method usually includes a two-step purification protocol (IMAC+GF) on ÄKTA Xpress. Purity and quality of the proteins is analysed by SDS-PAGE and Mass spectrometry is used to verify protein identity and identify possible inhomogeneities or modifications.

The Toronto Biotech team in also plays a key role in the SGC project to produce renewable antibodies to target proteins involved in Epigenetic signalling. The project is carried out in collaboration with Life Technologies and several lab groups that perform binder selections and cell-based validation experiments. The Biotech team tasks include cloning of expression constructs in a specific expression vector for antigen production, production of in vivo biotinylated antigens, re-cloning of selected binder candidates, production of in vivo biotinylated binder candidates for secondary validation, re-cloning of validated binders into IgG conversion vectors, production of IgG-like molecules using transient expression in mammalian cells and purification of IgG-like molecules.

Group Members

  • Peter Loppnau
  • Yanjun Li
  • Alma Seitova
  • Hao He
  • Nan Zhong
  • Elena Dobrovetsky
  • Mani Ravichandran
A roadmap to generate renewable protein binders to the human proteome.
Colwill K, Gräslund S
Nat. Methods. 2011 8(7):551-8. doi: 10.1038/nmeth.1607
PMID: 21572409

A secretory system for bacterial production of high-profile protein targets.
Kotzsch A, Vernet E, Hammarström M, Berthelsen J, Weigelt J, Gräslund S, Sundström M
Protein Sci.. 2011 20(3):597-609. doi: 10.1002/pro.593
PMID: 21308845

Generating a panel of highly specific antibodies to 20 human SH2 domains by phage display
Pershad K, Pavlovic JD, Gräslund S, Nilsson P, Colwill K, Karatt-Vellatt A, Schofield DJ, Dyson MR, Pawson T, Kay BK, McCafferty J.
Protein Eng Des Sel.. 2010 (4):279-88. doi: 10.1093/protein/gzq003
PMID: 20164216

Towards proteome scale antibody selections using phage display.
Mersmann M, Meier D, Mersmann J, Helmsing S, Nilsson P, Gräslund S, Colwill K, Hust M, Dübel S
N Biotechnol. 2010 27(2):118-28. doi: 10.1016/j.nbt.2009.10.007
PMID: 19883803

A pilot project to generate affinity reagents to human proteins.
Uhlen M, Gräslund S, Sundström M
Nat. Methods. 2008 5(10):854-5. doi: 10.1038/nmeth1008-854
PMID: 18825127

Protein production and purification.
Gräslund S, Nordlund P, Weigelt J, Hallberg BM, Bray J, Gileadi O, Knapp S, Oppermann U, Arrowsmith C, Hui R, Ming J, dhe-Paganon S, Park HW, Savchenko A, Yee A, Edwards A, Vincentelli R, Cambillau C, Kim R, Kim SH, Rao Z, Shi Y, Terwilliger TC, Kim CY, Hung LW, Waldo GS, Peleg Y, Albeck S, Unger T, Dym O, Prilusky J, Sussman JL, Stevens RC, Lesley SA, Wilson IA, Joachimiak A, Collart F, Dementieva I, Donnelly MI, Eschenfeldt WH, Kim Y, Stols L, Wu R, Zhou M, Burley SK, Emtage JS, Sauder JM, Thompson D, Bain K, Luz J, Gheyi T, Zhang F, Atwell S, Almo SC, Bonanno JB, Fiser A, Swaminathan S, Studier FW, Chance MR, Sali A, Acton TB, Xiao R, Zhao L, Ma LC, Hunt JF, Tong L, Cunningham K, Inouye M, Anderson S, Janjua H, Shastry R, Ho CK, Wang D, Wang H, Jiang M, Montelione GT, Stuart DI, Owens RJ, Daenke S, Schütz A, Heinemann U, Yokoyama S, Büssow K, Gunsalus KC
Nat. Methods. 2008 5(2):135-46. doi: 10.1038/nmeth.f.202
PMID: 18235434

The use of systematic N- and C-terminal deletions to promote production and structural studies of recombinant proteins.
Gräslund S, Sagemark J, Berglund H, Dahlgren LG, Flores A, Hammarström M, Johansson I, Kotenyova T, Nilsson M, Nordlund P, Weigelt J
Protein Expr. Purif.. 2007 58(2):210-21. doi: 10.1016/j.pep.2007.11.008
PMID: 18171622

2016

Apollo-NADP(+): a spectrally tunable family of genetically encoded sensors for NADP(.)
Cameron WD, Bui CV, Hutchinson A, Loppnau P, Gräslund S, Rocheleau JV
Nat. Methods. 15.02.2016 . doi: 10.1038/nmeth.3764
PMID: 26878383

2015

Streamlining the Pipeline for Generation of Recombinant Affinity Reagents by Integrating the Affinity Maturation Step.
Huang R, Gorman KT, Vinci CR, Dobrovetsky E, Gräslund S, Kay BK
Int J Mol Sci. 06.10.2015 16(10):23587-603. doi: 10.3390/ijms161023587
PMID: 26437402

Optimizing Production of Antigens and Fabs in the Context of Generating Recombinant Antibodies to Human Proteins.
Zhong N, Loppnau P, Seitova A, Ravichandran M, Fenner M, Jain H, Bhattacharya A, Hutchinson A, Paduch M, Lu V, Olszewski M, Kossiakoff AA, Dowdell E, Koide A, Koide S, Huang H, Nadeem V, Sidhu SS, Greenblatt JF, Marcon E, Arrowsmith CH, Edwards AM, Gräslund S
PLoS ONE. 05.10.2015 10(10):e0139695. doi: 10.1371/journal.pone.0139695
PMID: 26437229

A High Through-put Platform for Recombinant Antibodies to Folded Proteins.
Hornsby M, Paduch M, Miersch S, Sääf A, Matsuguchi T, Lee B, Wypisniak K, Doak A, King D, Usatyuk S, Perry K, Lu V, Thomas W, Luke J, Goodman J, Hoey RJ, Lai D, Griffin C, Li Z, Vizeacoumar FJ, Dong D, Campbell E, Anderson S, Zhong N, Gräslund S, Koide S, Moffat J, Sidhu S, Kossiakoff A, Wells J
Mol. Cell Proteomics. 19.08.2015 . doi: 10.1074/mcp.O115.052209
PMID: 26290498

Assessment of a method to characterize antibody selectivity and specificity for use in immunoprecipitation.
Marcon E, Jain H, Bhattacharya A, Guo H, Phanse S, Pu S, Byram G, Collins BC, Dowdell E, Fenner M, Guo X, Hutchinson A, Kennedy JJ, Krastins B, Larsen B, Lin ZY, Lopez MF, Loppnau P, Miersch S, Nguyen T, Olsen JB, Paduch M, Ravichandran M, Seitova A, Vadali G, Vogelsang MS, Whiteaker JR, Zhong G, Zhong N, Zhao L, Aebersold R, Arrowsmith CH, Emili A, Frappier L, Gingras AC, Gstaiger M, Paulovich AG, Koide S, Kossiakoff AA, Sidhu SS, Wodak SJ, Gräslund S, Greenblatt JF, Edwards AM
Nat. Methods. 29.06.2015 . doi: 10.1038/nmeth.3472
PMID: 26121405

Structural Basis for the Specificity of Human NUDT16 and Its Regulation by Inosine Monophosphate.
Trésaugues L, Lundbäck T, Welin M, Flodin S, Nyman T, Silvander C, Gräslund S, Nordlund P
PLoS ONE. 29.06.2015 10(6):e0131507. doi: 10.1371/journal.pone.0131507
PMID: 26121039

Tankyrase 1 Inhibitors with Drug-like Properties Identified by Screening a DNA-Encoded Chemical Library.
Samain F, Ekblad T, Mikutis G, Zhong N, Zimmermann M, Nauer A, Bajic D, Decurtins W, Scheuermann J, Brown PJ, Hall J, Gräslund S, Schüler H, Neri D, Franzini RM
J. Med. Chem.. 10.06.2015 . doi: 10.1021/acs.jmedchem.5b00432
PMID: 26061013

Identification of Structure-Activity Relationships from Screening a Structurally Compact DNA-Encoded Chemical Library.
Franzini RM, Ekblad T, Zhong N, Wichert M, Decurtins W, Nauer A, Zimmermann M, Samain F, Scheuermann J, Brown PJ, Hall J, Gräslund S, Schüler H, Neri D
Angew. Chem. Int. Ed. Engl.. 03.02.2015 . doi: 10.1002/anie.201410736
PMID: 25650139

Lysine Demethylase KDM4A Associates with Translation Machinery and Regulates Protein Synthesis.
Van Rechem C, Black JC, Boukhali M, Aryee MJ, Graslund S, Haas W, Benes CH, Whetstine JR
Cancer Discov. 06.01.2015 . doi: 10.1158/2159-8290.CD-14-1326
PMID: 25564516

2014

Recombinant renewable polyclonal antibodies.
Ferrara F, D'Angelo S, Gaiotto T, Naranjo L, Tian H, Gräslund S, Dobrovetsky E, Hraber P, Lund-Johansen F, Saragozza S, Sblattero D, Kiss C, Bradbury AR
MAbs. 20.12.2014 . doi: 10.4161/19420862.2015.989047
PMID: 25530082

Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.
Marcon E, Ni Z, Pu S, Turinsky AL, Trimble SS, Olsen JB, Silverman-Gavrila R, Silverman-Gavrila L, Phanse S, Guo H, Zhong G, Guo X, Young P, Bailey S, Roudeva D, Zhao D, Hewel J, Li J, Gräslund S, Paduch M, Kossiakoff AA, Lupien M, Emili A, Wodak SJ, Greenblatt J
Cell Rep. 10.07.2014 8(1):297-310. doi: 10.1016/j.celrep.2014.05.050
PMID: 24981860

Structural basis for phosphoinositide substrate recognition, catalysis, and membrane interactions in human inositol polyphosphate 5-phosphatases.
Trésaugues L, Silvander C, Flodin S, Welin M, Nyman T, Gräslund S, Hammarström M, Berglund H, Nordlund P
Structure. 06.05.2014 22(5):744-55. doi: 10.1016/j.str.2014.01.013
PMID: 24704254

A Basic Post-SET Extension of NSDs Is Essential for Nucleosome Binding In Vitro.
Allali-Hassani A, Kuznetsova E, Hajian T, Wu H, Dombrovski L, Li Y, Gräslund S, Arrowsmith CH, Schapira M, Vedadi M
J Biomol Screen. 04.03.2014 . doi: 10.1177/1087057114525854
PMID: 24595546

2013

Medium-Throughput Production of Recombinant Human Proteins: Protein Production in E. coli.
Burgess-Brown NA, Mahajan P, Strain-Damerell C, Gileadi O, Gräslund S
Methods Mol. Biol.. 10.11.2013 1091:73-94. doi: 10.1007/978-1-62703-691-7_5
PMID: 24203325

Substrate Specificity and Oligomerization of Human GMP Synthetase.
Welin M, Lehtiö L, Johansson A, Flodin S, Nyman T, Trésaugues L, Hammarström M, Gräslund S, Nordlund P
J. Mol. Biol.. 28.06.2013 . doi: 10.1016/j.jmb.2013.06.032
PMID: 23816837

2012

Expressing the human proteome for affinity proteomics: optimising expression of soluble protein domains and in vivo biotinylation.
Keates T, Cooper CD, Savitsky P, Allerston CK, Phillips C, Hammarström M, Daga N, Berridge G, Mahajan P, Burgess-Brown NA, Müller S, Gräslund S, Gileadi O
N Biotechnol. 15.06.2012 29(5):515-25. doi: 10.1016/j.nbt.2011.10.007
PMID: 22027370

Pan-pathway based interaction profiling of FDA-approved nucleoside and nucleobase analogs with enzymes of the human nucleotide metabolism.
Egeblad L, Welin M, Flodin S, Gräslund S, Wang L, Balzarini J, Eriksson S, Nordlund P
PLoS ONE. 25.05.2012 7(5):e37724. doi: 10.1371/journal.pone.0037724
PMID: 22662200

2011

Recombinant protein quality evaluation: proposal for a minimal information standard.
Buckle AM, Bate MA, Androulakis S, Cinquanta M, Basquin J, Bonneau F, Chatterjee DK, Cittaro D, Gräslund S, Gruszka A, Page R, Suppmann S, Wheeler JX, Agostini D, Taussig M, Taylor CF, Bottomley SP, Villaverde A, de Marco A
Stand Genomic Sci. 30.11.2011 5(2):195-7. doi: 10.4056/sigs.1834511
PMID: 22180821

A roadmap to generate renewable protein binders to the human proteome.
Colwill K, Gräslund S
Nat. Methods. 15.05.2011 8(7):551-8. doi: 10.1038/nmeth.1607
PMID: 21572409

A secretory system for bacterial production of high-profile protein targets.
Kotzsch A, Vernet E, Hammarström M, Berthelsen J, Weigelt J, Gräslund S, Sundström M
Protein Sci.. 11.02.2011 20(3):597-609. doi: 10.1002/pro.593
PMID: 21308845

2010

Towards proteome scale antibody selections using phage display.
Mersmann M, Meier D, Mersmann J, Helmsing S, Nilsson P, Gräslund S, Colwill K, Hust M, Dübel S
N Biotechnol. 31.05.2010 27(2):118-28. doi: 10.1016/j.nbt.2009.10.007
PMID: 19883803

Generating a panel of highly specific antibodies to 20 human SH2 domains by phage display
Pershad K, Pavlovic JD, Gräslund S, Nilsson P, Colwill K, Karatt-Vellatt A, Schofield DJ, Dyson MR, Pawson T, Kay BK, McCafferty J.
Protein Eng Des Sel.. 04.23.2010 (4):279-88. doi: 10.1093/protein/gzq003
PMID: 20164216

Generating a panel of highly specific antibodies to 20 human SH2 domains by phage display.
Pershad K, Pavlovic JD, Gräslund S, Nilsson P, Colwill K, Karatt-Vellatt A, Schofield DJ, Dyson MR, Pawson T, Kay BK, McCafferty J
Protein Eng. Des. Sel.. 17.02.2010 23(4):279-88. doi: 10.1093/protein/gzq003
PMID: 20164216

2009

Crystal structure of human diphosphoinositol phosphatase 1.
Thorsell AG, Persson C, Gräslund S, Hammarström M, Busam RD, Hallberg BM
Proteins. 09.07.2009 77(1):242-6. doi: 10.1002/prot.22489
PMID: 19585659

2008

A pilot project to generate affinity reagents to human proteins.
Uhlen M, Gräslund S, Sundström M
Nat. Methods. 01.10.2008 5(10):854-5. doi: 10.1038/nmeth1008-854
PMID: 18825127

The crystal structure of human cleavage and polyadenylation specific factor-5 reveals a dimeric Nudix protein with a conserved catalytic site.
Trésaugues L, Stenmark P, Schüler H, Flodin S, Welin M, Nyman T, Hammarström M, Moche M, Gräslund S, Nordlund P
Proteins. 04.09.2008 73(4):1047-52. doi: 10.1002/prot.22198
PMID: 18767156

The structure of the PP2A regulatory subunit B56 gamma: the remaining piece of the PP2A jigsaw puzzle.
Magnusdottir A, Stenmark P, Flodin S, Nyman T, Kotenyova T, Gräslund S, Ogg D, Nordlund P
Proteins. 12.07.2008 74(1):212-21. doi: 10.1002/prot.22150
PMID: 18618707

Structural and biophysical characterization of human myo-inositol oxygenase.
Thorsell AG, Persson C, Voevodskaya N, Busam RD, Hammarström M, Gräslund S, Gräslund A, Hallberg BM
J. Biol. Chem.. 30.05.2008 283(22):15209-16. doi: 10.1074/jbc.M800348200
PMID: 18364358

Protein production and purification.
Gräslund S, Nordlund P, Weigelt J, Hallberg BM, Bray J, Gileadi O, Knapp S, Oppermann U, Arrowsmith C, Hui R, Ming J, dhe-Paganon S, Park HW, Savchenko A, Yee A, Edwards A, Vincentelli R, Cambillau C, Kim R, Kim SH, Rao Z, Shi Y, Terwilliger TC, Kim CY, Hung LW, Waldo GS, Peleg Y, Albeck S, Unger T, Dym O, Prilusky J, Sussman JL, Stevens RC, Lesley SA, Wilson IA, Joachimiak A, Collart F, Dementieva I, Donnelly MI, Eschenfeldt WH, Kim Y, Stols L, Wu R, Zhou M, Burley SK, Emtage JS, Sauder JM, Thompson D, Bain K, Luz J, Gheyi T, Zhang F, Atwell S, Almo SC, Bonanno JB, Fiser A, Swaminathan S, Studier FW, Chance MR, Sali A, Acton TB, Xiao R, Zhao L, Ma LC, Hunt JF, Tong L, Cunningham K, Inouye M, Anderson S, Janjua H, Shastry R, Ho CK, Wang D, Wang H, Jiang M, Montelione GT, Stuart DI, Owens RJ, Daenke S, Schütz A, Heinemann U, Yokoyama S, Büssow K, Gunsalus KC
Nat. Methods. 01.02.2008 5(2):135-46. doi: 10.1038/nmeth.f.202
PMID: 18235434

2007

The use of systematic N- and C-terminal deletions to promote production and structural studies of recombinant proteins.
Gräslund S, Sagemark J, Berglund H, Dahlgren LG, Flores A, Hammarström M, Johansson I, Kotenyova T, Nilsson M, Nordlund P, Weigelt J
Protein Expr. Purif.. 22.11.2007 58(2):210-21. doi: 10.1016/j.pep.2007.11.008
PMID: 18171622

In situ proteolysis for protein crystallization and structure determination.
Dong A, Xu X, Edwards AM, Chang C, Chruszcz M, Cuff M, Cymborowski M, Di Leo R, Egorova O, Evdokimova E, Filippova E, Gu J, Guthrie J, Ignatchenko A, Joachimiak A, Klostermann N, Kim Y, Korniyenko Y, Minor W, Que Q, Savchenko A, Skarina T, Tan K, Yakunin A, Yee A, Yim V, Zhang R, Zheng H, Akutsu M, Arrowsmith C, Avvakumov GV, Bochkarev A, Dahlgren LG, Dhe-Paganon S, Dimov S, Dombrovski L, Finerty P, Flodin S, Flores A, Gräslund S, Hammerström M, Herman MD, Hong BS, Hui R, Johansson I, Liu Y, Nilsson M, Nedyalkova L, Nordlund P, Nyman T, Min J, Ouyang H, Park HW, Qi C, Rabeh W, Shen L, Shen Y, Sukumard D, Tempel W, Tong Y, Tresagues L, Vedadi M, Walker JR, Weigelt J, Welin M, Wu H, Xiao T, Zeng H, Zhu H
Nat. Methods. 04.11.2007 4(12):1019-21. doi: 10.1038/nmeth1118
PMID: 17982461

Crystal structure of human cytosolic 5'-nucleotidase II: insights into allosteric regulation and substrate recognition.
Walldén K, Stenmark P, Nyman T, Flodin S, Gräslund S, Loppnau P, Bianchi V, Nordlund P
J. Biol. Chem.. 15.06.2007 282(24):17828-36. doi: 10.1074/jbc.M700917200
PMID: 17405878

Crystal structure of human inosine triphosphatase. Substrate binding and implication of the inosine triphosphatase deficiency mutation P32T.
Stenmark P, Kursula P, Flodin S, Gräslund S, Landry R, Nordlund P, Schüler H
J. Biol. Chem.. 02.02.2007 282(5):3182-7. doi: 10.1074/jbc.M609838200
PMID: 17138556

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