Melanie Higgins

Melanie  Higgins

Assistant Professor


Education

B.Sc. (Honors), Biochemistry, University of Victoria, Canada, 2006

Ph.D., Biochemistry, University of Victoria, Canada, 2012

Postdoctoral research: University of Adelaide, Australia, 2013-2014

Postdoctoral research: University of British Columbia, Canada 2015-2021

Research Interests

Microbes can impact human health in a number of different ways, the most obvious is by having a direct influence like with the microbiota or pathogens. Microbes can also help to improve human health indirectly by using microbial components for more application based technologies. The Higgins lab aims to understand microbial processes that have both direct and indirect effects on human health.

Host glycan metabolism by gut microbiota: There are trillions of bacteria that live inside the human body, and are collectively referred to as the microbiota. Many exhibit a positive outcome and have important roles in human health, such as aiding in digestion, supplying vital nutrients, and promoting normal development of immune functions. The microbiota is extremely complex and imbalances in its composition can drastically influence the health of the host and lead to serious disease or infection. Thus, studying the dynamics between commensal bacteria and host is of particular interest to gain a better understanding of the mechanisms that these bacteria use to impose a positive health outcome. In turn, this can allow for the manipulation of these mechanisms and/or dynamics to select for optimal microbiota composition to maintain the health of the individual or to repair an imbalance in composition to restore the health of the individual.

The Higgins lab studies the mechanisms by which commensal bacteria interact with host glycans in the gastrointestinal tract. We identify and characterize enzymes involved in the degradation of host mucin, glycocalyx, and glycans found in breast milk using in vitro techniques such as biochemical assays and X-ray crystallography. We are also interested in determining the biological roles of host glycan metabolism in colonization and/or gut-barrier function, using in vivo techniques including cell-based assays and animal models.

Natural products and their biosynthesis: Microorganisms play an important role in our everyday lives and provide essential functions such as recycling of living material, nitrogen fixation, and symbiotic colonization with animals. The ability of microorganisms to live in a wide variety of environments has led to the evolution of countless secondary metabolites, or natural products, required for their survival. These metabolites have long been utilized for many different applications from food preservatives and flavoring agents to biofuels. More notably, natural products commonly have bioactive properties which can be exploited as pharmaceutical products like antibiotics and antitumor agents.

The Higgins lab investigates how natural products are biologically synthesized by determining the structure-function relationships of the individual biosynthetic enzymes. We also use genome mining to identify novel natural products produced by uncharacterized gene clusters to discover new molecules and biosynthetic enzymes. These projects will lay the groundwork for protein- and bio-engineering approaches for diversification of natural products to improve and/or broaden their therapeutic potential and for clinical development strategies.

 

Selected Publications

Higgins MA, Ryan KS. Generating a fucose permease deletion mutant in Bifidobacterium longum subsp. infantis ATCC 15697. (2021) Anaerobe. 68:102320. DOI: 10.1016/j.anaerobe.2021.102320.

 

Higgins MA, Tegl G, MacDonald SS, Arnal G, Brumer H, Withers SG, Ryan KS. N-Glycan degradation pathways in gut- and soil-dwelling Actinobacteria share common core genes. (2021). ACS Chem Biol. 16(4):701-711. DOI: 10.1021/acschembio.0c00995.

 

Guo J, Higgins MA, Daniel-Ivad P, Ryan KS. An asymmetric reductase that intercepts acyclic imino acids produced in situ by a partner oxidase. (2019) J Am Chem Soc. 141(31):12258-12267. DOI: 10.1021/jacs.9b03307.

 

Du YL, Higgins MA, Zhao G, Ryan KS. (2019) Convergent biosynthetic transformations to a bacterial specialized metabolite. Nat Chem Biol. 15(11):1043-48. DOI: 10.1038/s41589-019-0331-5.

 

Du YL, He HY, Higgins MA, Ryan KS. (2017) A heme-dependent enzyme forms the nitrogen-nitrogen bond in piperazate. Nat Chem Biol. 13(8):836-838. DOI: 10.1038/nchembio.2411.