Understanding and harnessing natural variation in adaptability

The rise of antimicrobial resistance is an urgent global threat to human health and global healthcare capacities.

Despite ongoing efforts to develop new antimicrobial drugs, eventual adaptation is an inevitable corollary of evolution.

Long-term solutions therefore require innovative approaches, including (1) learning to predict adaptation and (2) developing platforms to screen strategies against microbial adaptation.

The capacity of an organism to adapt to new environments, also described as adaptability, is a heritable trait that varies substantially between even closely related lineages.

Dissecting the genetic basis and mechanisms driving variation in adaptability is the critical first step in achieving these long-term objectives.As an MCSA fellow, Dr Xanita Saayman will receive training from Dr Gianni Liti at the Institute for Research in Cancer and Ageing (IRCAN) and from Dr Jonas Warringer during a secondment to the University of Gothenburg.

Throughout NAT-ADAPT, Dr Saayman will exploit an extensive collection of Saccharomyces cerevisiae isolates with unprecedented scales of phenotypic and genotypic diversity.

Bridging interdisciplinary fields (e.g., population genetics, phenomics, genomics, genome engineering), NAT-ADAPT will identify and characterise genetic drivers of adaptability, harnessing this knowledge for two applications.

First, NAT-ADAPT will model adaptation dynamics based on quantifiable genome properties, serving as an invaluable resource for predicting the emergence of antimicrobial resistance. Second, NAT-ADAPT will produce ‘hyper-evolver’ Saccharomyces cerevisiae strains.

Such strains can serve as critical platforms with which to screen strategies against microbial adaptation, improving the efficacy of current antimicrobial solutions.