Lyann Sim

Lyann pic

Research Associate

2013-2015 Postdoctoral Fellow, Ryerson University, Toronto. (Prof. W. Wakarchuk)

2010-2013 Research Scientist, Carlsberg Laboratory, Denmark. (Prof. A. Henriksen & Prof. M. Palcic)

2004-2010 Ph.D., Medical Biophysics, University of Toronto. (Prof. D. Rose)

2000-2004 B.Sc. (Hons) Biochemistry, University of British Columbia

 

Email: lsim(at)chem.ubc.ca

NCE 324

(604) 822-9300

 

INTERESTS

My research interests revolves around carbohydrate active enzymes and how we can apply and tailor their activities for use in therapeutic and industrial applications.  To increase the efficiency in protein engineering, I am approaching this problem using a rational protein design strategy as well as a directed evolution approach. This requires a clear understanding of the structure and function of the target enzyme, as well as high-throughput assay methodology to screen for enhanced mutants.

 

I am working on a project in collaboration with the Wakarchuk lab (Ryerson University) to introduce O-glycosylation machinery into E. coli. As glycosylation is a crucial property of many therapeutic proteins and can extend its circulation half-life, it is beneficial to add these glycans during the production of these proteins.  As an alternative to costly mammalian cell systems which allows for glycosylation, we are aiming to engineer an E. coli strain that is capable of adding simple O-linked sugars. This will be accomplished by introducing into E. coli, various engineered glycosyltransferases capable of T-antigen synthesis. The engineering work will include improving the functionality of the mammalian and bacterial core 1 synthase through directed evolution approaches.

 

PUBLICATIONS

https://scholar.google.ca/citations?user=W_OOZVUAAAAJ&hl=en

Selected publications

  • Møller MS*, Windahl MS*, Sim L*, Bøjstrup M, Abou Hachem M, Hindsgaul O, Palcic M, Svensson B, Henriksen A (2015). Oligosaccharide and substrate binding in the starch debranching enzyme barley limit dextrinase. J. Mol. Biol. 427. 1263-77.
  • Sim L, Beeren SR, Findinier J, Dauvillee D, Ball S, Henriksen A, Palcic M (2014). Crystal structure of the Chlamydomonas starch debranching enzyme isoamylase ISA1 reveals insights into the mechanism of branch trimming and complex assembly. J. Biol. Chem. 289. 22991-3003.
  • Sim L, Willemsma C, Pinto BM, Rose DR (2010). Structural basis for substrate selectivity in human GH31 intestinal glucosidases: Comparison of N-terminal maltase-glucoamylase and sucrase-isomaltase. J. Biol. Chem. 285, 17763-70.
  • Sim L, Jayakanthan K, Mohan S, Nasi R, Johnston BD, Pinto BM, Rose DR (2010). New glucosidase inhibitors from an Ayurvedic herbal treatment for type 2 diabetes: structures and inhibition of human intestinal maltase-glucoamylase with compounds from Salacia reticulata. Biochemistry 49, 443-451.
  • Sim L, Quezada-Calvillo R, Sterchi EE, Nichols BL, Rose DR (2008). Human Intestinal Maltase-Glucoamylase: Crystal Structure of the N-terminal Catalytic Subunit and Basis of Inhibition and Substrate Specificity. J. Mol. Biol. 375, 782-92.
  • Rossi EJ*, Sim L*, Kuntz DA, Hahn D, Johnston BD, Ghavami A, Szczepina MG, Kumar NS, Sterchi EE, Nichols BL, Pinto BM, Rose DR (2006). “Inhibition of recombinant human maltase glucoamylase by salacinol and derivatives.”  FEBS J. 273, 2673-83.