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My research group utilizes metabolic & enzyme engineering to investigate and customize novel biosynthetic enzymes that can convert biomass-derived feedstocks into value-added chemicals. We have published highly acclaimed papers on model-guided enzyme engineering, process development, enzyme discovery using metagenomics and engineering metabolic control schemes that bridge with bioprocess control and improve productivity. Each of these works represents a critical advance in our ability to employ engineered microorganisms as a manufacturing platform. We also extend the principles of metabolic engineering to the design and development of unique bioremediation strategies to rehabilitate the water quality in and around industrial zones and new mining technologies and we are currently collaborating with Suncor and Jetti Resources, respectively, to deploy novel biotechnologies in the field. In addition to green engineering, my research group also pursues medical biotechnology research, and focuses on three stages in the drug discovery life cycle – (1) bioengineering for assay development, (2) biosynthetic engineering for lead generation, and (3) pharmaceutical product development. Our work on bioengineered assays aims to assemble three-dimensional, structured brain organoids from human pluripotent stem cells for use in pre-clinical screening of hits against Alzheimer’s disease. Through this work, we have established a formal collaboration with STEMCELL Technologies. Our work on pharmaceutical product development is advancing a concept that we dub ‘medicine-by-design’, a fast and low-cost methodology to advance a drug molecule from concept to formulated product based on the synergistic application of bioinformatics and data analysis, metabolic engineering and formulation science. We work closely with an industrial partner, InMed Pharmaceuticals, and have successfully advanced two projects to clinical testing. Our work on development of a ‘smart’ contact lens for treating glaucoma is among the most read scientific articles of 2018. Similarly, our work on the development of a printable bandage for healing damaged skin in patients suffering from Epidermolysis Bullosa Simplex (EBS) is currently under consideration for publication. Both works are the subjects of patent filings. We have recently initiated a new line of research in the group that fuses biology and materials science to develop better materials and transcend current limitations in manufacturing. The synergistic combination of biological systems with abiotic, functional materials that greatly improves the properties of the original host, and the resulting systems can be applied to a wealth of manufacturing, energy and environmental remediation applications. We laid the intellectual foundations of this paradigm in a forum article in Trends in Biotechnology and subsequently published a proof-of-concept study on a biohybrid photovoltaic cell that is the best in its class and could be used in bioorganic optoelectronics. My research group currently collaborates with 7 companies – STEMCELL Technologies, InMed Pharmaceuticals, Jetti Resources, Metabolik Technologies, Sanofi Pasteur, Reliance Industries Limited and Phytonix Corporation.
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Great Supervisor Week Mentions
Taking this chance #GreatSupervisor occasion at #UBC to express my thanks to Vikramaditya Yadav @biofoundry. He is an incredible mentor, and brilliant person. I am so grateful for all of your support.
I am privileged to have the best and most supportive supervisor. I have learned a lot from you, whether it is dealing with stress or asking critical questions; whether it’s research or teaching. @biofoundry is #GreatSupervisor at #UBC also a great friend and mentor.
Graduate Student Supervision
Doctoral Student Supervision (Jan 2008 - Nov 2019)
No abstract available.
Master's Student Supervision (2010 - 2018)
Biocatalyst discovery is integral to bioeconomy development, enabling design of scalable bioprocesses that can compete with the resource-intensive petrochemical industry. Uncultivated microbial communities within natural and engineered ecosystems provide a near-infinite reservoir of genomic diversity and metabolic potential that can be harnessed for this purpose. To bridge the cultivation gap, functional metagenomic screens have been developed to recover active genes directly from environmental samples. In this thesis, a pipeline for recovery of biomass-deconstructing biocatalysts sourced from pulp and paper mill sludge (PPS) metagenome is described. This environment is targeted given its high composition of cellulose that is hypothesized to direct enrichment of enzymes capable of hydrolysing it. The resulting oligosaccharides represent platform molecules that can be fed to downstream applications using consolidated process design for converting biological waste streams into value-added products. High-molecular weight DNA was extracted from sludge and used to construct a fosmid library containing 15,000 clones using the copy control system in EPI300™-T1 R E.coli. Extracted DNA was also used in whole genome shotgun sequencing to compare the metabolic potential of the sludge community with fosmid screening outcomes as well as other waste biomass environments using MetaPathways v2.5 software pipeline, with specific emphasis on carbohydrate-active enzymes (CAZymes). Metagenomic assembling, open reading frame (ORF) prediction, binning and taxonomic assignment approaches were also used to bring out correlations between function and taxonomy. In total, 32,232 ORF’s were mapped to the CAZy database predicted to encode glycoside hydrolases, glycosyl transferases, and carbohydrate binding module families. The fosmid library was screened for glycosidase hydrolase activities using a pool of sensitive fluorogenic glycosides of 6-chloro-4-methylumbelliferone (CMU). A total of 744 clones capable of converting pooled substrates were recovered indicating an extremely high hit rate (1 hit per 43 clones). Following fosmid sequencing and annotation, two of the most promising hits with defined single GH family loci were sub-cloned and overexpressed in E.coli BL21 DE3 strain to conduct basic biochemical characterization. Activity of purified enzymes was demonstrated on model lignocellulosic substrates to evaluate the potential of implementing the proposed circular bioprocess with waste PPS as both the feedstock and source of enriched biocatalysts.
Big problems, tiny solutions (29 Apr 2019)