William Harcombe
University of Minnesota, MN·Ecology & Evolution
Organisms in a changing world rarely face one problem at a time: heat and drought, or two drugs at once. Predicting the combined effect is hard, because one stress can change how damaging another is.
- Fields
Ecology & Evolution
Microbiology & Immunology
Biology
- Topics
mutualism
cross-feeding
Escherichia coli
- Grants
- 1 known grant, through Aug 2028
What they work on
- Test whether mutualism changes the combined effect of antibiotic pairs by running over 3,900 growth experiments comparing Escherichia coli and Salmonella enterica in monoculture versus obligate cross-feeding co-culture.
- Determine how species interactions alter the rate and genetic mechanisms of evolved resistance to multiple stresses, using over 150 evolution experiments in monoculture and in mutualistic co-culture.
- Use genome-scale metabolic models, which simulate all metabolic reactions in a cell, to predict how drug combinations propagate through metabolite exchange between the two partner bacteria.
- Build predictive tools for combined-stress outcomes in mutualisms by integrating the growth and evolution data with steppingstone models of evolutionary paths and clustering algorithms.
More about the research
The puzzle gets harder when species depend on each other, since a stress that hits one partner indirectly hits the other. Mutually beneficial partnerships (mutualisms) underpin everything from crop production to global nutrient cycling, so this project asks whether their response to combined stresses can be predicted at all.
Why it matters
Drug combinations are used partly to slow the evolution of antibiotic resistance, but most predictions ignore that bacteria in the body and the environment live in metabolically interdependent communities. Showing how interdependence changes whether two drugs work together, and how fast resistance arises, could improve how combination treatments are chosen. The same framework could help forecast how mutualisms important to agriculture and nutrient cycling respond to multiple simultaneous stresses.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Michael Manhart
Rutgers University-New Brunswick, NJ·Ecology & Evolution
Test whether cross-feeding different nutrient types (amino acids, vitamins, carbon intermediates) changes the fitness effects of mutations differently, using engineered E. coli auxotroph partnerships and DNA-barcoded mutant libraries.
Sergey Kryazhimskiy
University of California-San Diego, CA·Ecology & Evolution
Develop mathematical theory for how the biochemical architecture of cells, starting with complex metabolic networks, constrains the shape of fitness landscapes and how mutations move organisms across them.
Rasika Harshey
University of Texas at Austin, TX·Microbiology & Immunology
Use phage Mu transposition, which inserts DNA almost anywhere, to build a high-resolution map of contacts between genomic loci in E. coli and test how genome organization influences gene expression.
The school
University of Minnesota: 88 labs on PI Pages, $1.4B a year on research, 722 research doctorates a year.
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