Jeff Hasty
University of California-San Diego, CA·Biomedical Engineering
Bacteria can be programmed like machines. By inserting designed pieces of DNA, called genetic circuits, into a bacterium, it can be made to sense something in its surroundings and respond in a chosen way.
- Fields
Biomedical Engineering
Biology
Microbiology & Immunology
- Topics
synthetic biology
genetic circuits
living biosensors
- Grants
- 2 known grants, through Aug 2029
What they work on
- Identify naturally competent gut microbes, bacteria that take up surrounding DNA, from patient samples, to serve as an oxygen-free-tolerant sensor host better suited to the gut than the current chassis Acinetobacter baylyi.
- Improve DNA-sensing genetic circuits to detect cancer mutations, by tuning them for the new bacterial host, reducing background mutation rates and adding multiplex detection of additional hotspot variants including pancreatic cancer mutations.
- Engineer a urine-detectable diagnostic output that is produced when the biosensor bacteria sense tumor DNA or blood in the gut.
- Characterize biosensor performance inside the living gastrointestinal tract using mouse models with tumors implanted in the colon and pancreas that mimic human disease.
- Generate phenotypic variation within a genetically identical bacterial population by linking the copy numbers of two co-transformed plasmids, and test whether such strains retain their adapted state after the stimulus is removed.
- Build a multi-dimensional microfluidic device to observe how engineered bacterial colonies pattern themselves across gradients of tumor-relevant small molecules.
- Engineer an ultrasound-activated toggle switch that shifts engineered bacteria from low-density growth to high-density population cycling, and test it in colorectal tumor spheroids.
More about the research
Two threads of work run through this lab: building living bacterial sensors that detect cancer DNA inside the gut, and developing the general engineering rules and computational models needed to make engineered bacteria behave predictably in messy, uneven environments such as tumors.
Why it matters
Earlier detection of colorectal and pancreatic cancer saves lives, but screening today is invasive, expensive or nonexistent. A bacterium that senses tumor DNA in the gut and reports it through a urine test could make screening far less burdensome than colonoscopy, raise participation, catch these cancers sooner and cut healthcare costs. The parallel engineering work could make bacteria that grow preferentially inside solid tumors into controllable, programmable living therapies.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Michael Baym
Harvard University, MA·Microbiology & Immunology
Test whether the standard model of resistance evolution is incomplete by measuring the direct and indirect fitness costs of resistance and of specialization in evolving bacterial populations under tunable antibiotic selection.
Maria Pena
University of South Carolina-Columbia, SC·Medicine & Clinical Research
Identify developmental windows, from before birth through childhood, when exposure to commonly prescribed pediatric antibiotics most increases colorectal cancer risk, using mouse models of colorectal cancer.
Wantong Yao
University of Texas MD Anderson Cancer Center, TX·Medicine & Clinical Research
Define the molecular pathways through which a newly identified stress-response regulator helps pancreatic ductal adenocarcinoma (PDAC) cells survive nutrient shortage, low oxygen and oxidative stress, and evade the immune system.
The school
University of California-San Diego: 84 labs on PI Pages, $1.9B a year on research, 637 research doctorates a year.
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