We live in a microbial world
Both in terms of total mass and species diversity, bacteria vastly outnumber all animals on Earth! Humans are surrounded by extremely complex communities of microorganisms that live out in nature and in the artificial environments we build. In fact, we know that our bodies naturally harbor trillions of microbial cells in our gut and on our skin. The vast majority of the organisms in this microbial world either promote our health, or do not affect us. However, some of these organisms are opportunistic pathogens that can cause disease in certain circumstances. Antibiotics are used to treat these opportunistic infections, but unfortunately many pathogens are becoming increasingly resistant to these life saving drugs. Ultimately, if we want to manipulate our microbiota to promote health, or develop next generation antibiotics, we must fundamentally understand how bacterial cells work. The Saunders Lab aims to advance our understanding of the bacterial domain of life using high throughput genetics to map the molecular interactions that underly cellular physiology.
Typically, strategies for modifying bacterial genomes take one of two approaches. Reverse genetics enables very accurate modifications, but is typically low throughput (e.g. GFP fusion). Forward genetics enables modifications to be made at high throughput across the genome, but these techniques are random and therefore imprecise (e.g. transposon mutagenesis).
What if we could perform bacterial genetics with high throughput and high accuracy?
Designer mutant libraries
The Saunders Lab will develop new genetic techniques for precisely constructing mutant libraries at high throughput. Genomic modifications can be specified by short DNA oligos that encode homology to different positions in bacterial genomes. With modern DNA synthesis, tens of thousands of oligos can be computationally designed and ordered routinely. Therefore mutant libraries can be designed and constructed to ask new questions about bacteria at genomic scales.
Genes and proteins do not work alone, but instead these components interact to form complex and dynamic networks that determine cellular physiology. Accurate and high throughput tools will enable the construction of double mutant and combinatorial libraries that can be used to measure interactions between cellular components.