[9] Collins graduated from Holy Cross in 1987 as class valedictorian, receiving a Bachelor of Arts (BA) in physics, summa cum laude.
[11] At Oxford, he was a member of Balliol College and earned a Doctor of Philosophy (DPhil) in 1990 specializing in medical and mechanical engineering.
[18] He was the first (along with Michael Elowitz and Stanislas Leibler) to show that one can harness the biophysical properties of nucleic acids and proteins to create biological circuits, which can be used to rewire and reprogram living cells.
In a paper published in Nature,[19] Collins designed and constructed a genetic toggle switch – a synthetic, bistable gene regulatory network – in E. coli.
The toggle switch forms a synthetic, addressable cellular memory unit with broad implications for biophysics, biomedicine and biotechnology.
[18] Building on this work, Collins showed that synthetic gene networks can be used as regulatory modules and interfaced with a microbe's genetic circuitry to create programmable cells for a variety applications,[21] e.g., synthetic probiotics to serve as living diagnostics and living therapeutics to detect, treat and prevent infections such as cholera and C.
[36][37][38] Recently, Collins developed freeze-dried, cell-free synthetic gene circuits, an innovative platform that forms the basis for inexpensive, paper-based diagnostic tests for emerging pathogens (e.g., Zika, Ebola, SARS-CoV-2, antibiotic-resistant bacteria),[39][40][41][42] wearable biosensors,[43] and portable biomolecular manufacturing (e.g., to produce vaccine antigens) in the developing world.
[52] Collins is also one of the leading researchers in systems biology through the use of experimental-computational biophysical techniques to reverse engineer and analyze endogenous gene regulatory networks.
[53] Collins and collaborators showed that reverse-engineered gene networks can be used to identify drug targets, biological mediators and disease biomarkers.
[54] Collins and collaborators discovered, using systems biology approaches, that all classes of bactericidal antibiotics induce a common oxidative damage cellular death pathway.
This work established a mechanistic relationship between bacterial metabolism and antibiotic efficacy, which was further developed and validated by Collins and his team in a series of follow-on studies.
[57] Additionally, Collins and co-workers discovered that sublethal levels of antibiotics activate mutagenesis by stimulating the production of reactive oxygen species, leading to multidrug resistance.
[58] Collins and colleagues, using their systems approaches, also discovered a population-based resistance mechanism constituting a form of kin selection whereby a small number of resistant bacterial mutants, in the face of antibiotic stress, can, at some cost to themselves, provide protection to other more vulnerable, cells, enhancing the survival capacity of the overall population in stressful environments.
[59] In 2020, Collins was part of the team—with fellow MIT Jameel Clinic faculty lead Professor Regina Barzilay—that announced the discovery through deep learning of halicin, the first new antibiotic compound for 30 years, which kills over 35 powerful bacteria, including antimicrobial-resistant tuberculosis, the superbug C. difficile, and two of the World Health Organization's top-three most deadly bacteria.
[61] Collins also pioneered the development and use of nonlinear dynamical approaches to study, mimic and improve biological function,[62] expanding our ability to understand and harness the physics of living systems.
[66] This work has led to the creation of a new class of medical devices to address complications resulting from diabetic neuropathy, restore brain function following stroke, and improve elderly balance.