- Postdoctoral Research, University of British Columbia, Canada, 2015-2021
- Postdoctoral Research, University of Adelaide, Australia, 2013-2014
- PhD, Biochemistry, University of Victoria, Canada, 2012
- BS (Honors), Biochemistry, University of Victoria, Canada, 2006
Microbes can impact human health in a number of different ways, the most obvious way is by having a direct influence like 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.
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 uses specialized genome mining approaches to identify novel glycosylated natural products produced by uncharacterized gene clusters to discover new molecules and biosynthetic enzymes. We also investigate how natural products are made by determining the structure-function relationships of the individual biosynthetic enzymes. This 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. This project is funded by NIH 1R35GM151137-01.
Glycans are the most abundant biopolymers in nature and have immense structural complexity. As such, they are involved in virtually all physiological processes, such as protein folding, nutritional storage, adhesins, and receptors. Both pathogenic and commensal bacteria have evolved many different mechanisms to degrade glycans. Since glycan structures are so diverse and there are countless bacterial species present in nature, researchers have only begun to scratch the surface of how bacteria degrade complex carbohydrates.
The Higgins lab studies how bacteria degrade glycans from different environments. We are interested in the mechanisms by which specific commensal bacteria interact with host glycans in the gastrointestinal tract. We are also looking to identify new carbohydrate-active enzyme activities from diverse sources.
- 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.