Life healing life
Our CATCH technology engineers cells to detect and discriminate cell free DNA. This may be of value in clinical (cancer and infection) and commercial (ecology, industrial) applications – wherever and whenever, the detection of DNA is valuable.
Engineered naturally competent Acinetobacter baylyi to detect donor DNA from the genomes of colorectal cancer (CRC) cells.
Synthetic biology has developed sophisticated cellular biosensors to detect and respond to human disease. However, biosensors have not yet been engineered to detect specific extracellular DNA sequences and mutations. Here, we engineered naturally competent Acinetobacter baylyi to detect donor DNA from the genomes of colorectal cancer (CRC) cells, organoids, and tumors. We characterized the functionality of the biosensors in vitro with co-culture assays and then validate in vivo with sensor bacteria delivered to mice harboring colorectal tumors. We observe horizontal gene transfer from the tumor to the sensor bacteria in our mouse model of CRC. This Cellular Assay for Targeted, CRISPR-discriminated Horizontal gene transfer (CATCH) enables the biodetection of specific cell-free DNA.
Who is CATCH?
Meet the team
Dr Dan Worthley
Dan Worthley
During Dan’s studies he decided that he wanted to become a clinician-scientist, balancing a busy clinical practice with an exciting research program. Therefore, after becoming a gastroenterologist, he completed a PhD and MPH in cancer prevention, and then to Columbia University in New York for his post-doctoral fellowship. In New York, Dan worked very closely with Professor Siddhartha Mukherjee. Sid kept on telling Dan about a future where disease would be detected and cured with cells, not pills.
As a gastroenterologist, the most obvious cells to start engineering were the microbes that already live within us. Dan returned to Brisbane to work at Colonoscopy Clinic, inspired by the Clinic’s vision of a future where no Australian dies of colorectal cancer. But, in order to reach that goal, Dan has continued to develop research projects to invent and apply new technologies. He was fortunate to meet and now work very closely with Jeff Hasty.
Dan’s major achievements have been in stem cell biology, inherited gastrointestinal cancer syndromes such as GAPPS, and translating scientific discoveries into the clinic, with a focus now on luminal care.
CATCH Dan at dan@colonoscopyclinic.com.au
A complete list of Dan’s published work can be found at
https://www.ncbi.nlm.nih.gov/myncbi/16SDeUEUD-ZQq/bibliography/public/
PROFESSOR JEFF HASTY
Jeff Hasty
Somewhere during Jeff’s postdoctoral fellowship with Professor Jim Collins, he mutated from a theoretical physicist into a hybrid computational and molecular biologist. This led Jeff to become a pioneer and leader in the field of synthetic biology, the engineering of genetic circuits in living cells.
He is a fellow of the American Institute for Medical and Biological Engineering and has applied his basic discoveries in synthetic biology, mathematics and engineering to cancer detection and treatment, amongst other target areas. He is currently at the University of California, San Diego, where he is a Professor in the Departments of Molecular Biology and Bioengineering, Director of the BioCircuits Institute, and Co-Director of the UCSD qBio Ph.D Specialization Program.
His major scientific achievements have been in the fields of Synthetic and Systems Biology particularly in the design of synthetic gene regulatory and signalling networks, alongside the technical development of microfluidic technologies. Cells, constructs, and microfluidic devices from his lab are in use for research and teaching around the world and have spawned several start-up companies.
CATCH Jeff at hasty@ucsd.edu
A complete list of Jeff’s published work can be found at
https://www.ncbi.nlm.nih.gov/sites/myncbi/jeff.hasty.1/collections/58821505/public/
A/PROF. SUSI WOODS
Susan Woods
Susi leads the Gut Cancer research group at the University of Adelaide and the South Australian Health & Medical Research Institute in 2019 as a Beat Cancer SA fellow.
Susi trained with Nobel Laureate J. Michael Bishop at University of California San Francisco, Prof Nick Hayward at QIMR-B in Brisbane, Australia and Daniel Worthley at SAHMRI, specialising in functional testing of (epi)genetic alterations found in cancer. Almost 10,000 Australians die from gut cancers each year.
Research in Susi’s group aims to improve early detection methods and treatments for these cancers using preclinical models developed by Susi’s team and patient derived samples. Susi works with leading synthetic biologists and microbial ecologists to develop engineered bacterial strains for cancer detection and tumour specific treatment delivery.
Susi’s group also uses genomics and patient tissue samples grown in the lab (as organoids) to assess the clinical utility of this approach in guiding choice of personalised treatments.
CATCH Susi at susan.woods@adelaide.edu.au
A complete list of Susan’s published work can be found at
https://www.ncbi.nlm.nih.gov/myncbi/susan.woods.3/bibliography/public/
DR JOSEPHINE WRIGHT
Dr Josephine Wright
Jo completed a PhD in Biochemistry at the University of Adelaide, South Australia followed by a post-doctoral fellowship at University of Bath before returning to Adelaide to build a career focussed on cancer treatment.
With her breadth of experience across a range of fields, Jo was drawn to the opportunity to blend her knowledge and skills with gastrointestinal cancer research aimed at providing targeted treatment with rapid clinical application working with Dan Worthley and Susi Woods at the South Australian Health & Medical Research Institute, SAHMRI.
Jo is passionate about research, training the next generation of scientists and making an impact in the treatment of gastrointestinal cancers.
A complete list of Jo’s published work can be found at:
Dr Robert Cooper
Robert Cooper
Rob studied physics at Williams College before deciding he wanted to work on biophysics, which became molecular biology for a PhD at Princeton University, and then synthetic biology for postdoctoral and subsequent research with Jeff Hasty at UC San Diego.
Rob is drawn to questions in biology that can be solved with a quantitative modelling approach, and he keeps an eye out for ways to make something useful. He stumbled into horizontal gene transfer when his bacteria began expressing genes they weren’t supposed to have, and he has been building a research program around the phenomenon since.
Rob was fortunate to meet Dan Worthley, who shared the question of “What could we use this for?” and helped form a collaboration with cancer experts Susi Woods and Jo Wright.
A complete list of Robert’s published work can be found at:
https://www.ncbi.nlm.nih.gov/myncbi/robert.cooper.2/bibliography/public/
Questions?
If you have any questions please email us at hello@catch.contact