James J. Collins

Boston University (1990–2014)

After receiving his doctorate, Collins joined the faculty of Boston University (BU) in 1990.^[2] One of his early research focuses included kinesiology; he developed a series of devices to improve locomotion, neural function, and cardiac function, including vibrating insoles.^[2] He was appointed a professor of biomedical engineering at the Boston University College of Engineering, where he co-founded the Center for BioDynamics in 1997 and served as its director,^[14] and earned multiple recognitions for teaching, including being named the college's "Biomedical Engineering Teacher of the Year" and the university's "Professor of the Year".^[15] He won the university's Metcalf Cup and Prize for Excellence in Teaching in 2000, the university's highest teaching honor.^[15][16] While at BU, he simultaneously taught at Harvard Medical School from 1998 to 2010.^[14]

In 1999, Collins, along with his biomedical engineering student Timothy Gardner, executed one of the first attempts to engineer genomes to perform certain functions. Together, they edited the genes of E. coli bacteria to create or stop creating certain proteins. Their findings of a genetic on/off, or "toggle switch," were published in Nature in an article now considered seminal in the field of synthetic biology.^[17] In October 2003, he became the first bioengineer to be awarded a MacArthur Fellowship,^[18] which he received for "identifying abstract principles underlying complex biological phenomena such as motor control during standing and walking".^[19][20] That same year, he was the director of the Applied Biodynamics Laboratory at BU.^[20] In 2008, he was named a principal investigator of the Howard Hughes Medical Institute—the first from Boston University—to pursue research in gene expression and antibiotic resistance in single cells.^[21] On May 18, 2009, he was appointed as one of BU’s two inaugural William F. Warren Distinguished Professors, alongside George Annas.^[15] In 2010, he was appointed by President Barack Obama to the Presidential Commission for the Study of Bioethical Issues.^[22]

By 2011, Collins held five appointments at Boston University: William F. Warren Distinguished Professor, University Professor, Professor of Biomedical Engineering, Professor of Medicine, and co-director of the Center for BioDynamics.^[23] That same year, he became the third BU professor to be elected to the National Academy of Engineering; by that time, his research focused on the invention of synthetic gene networks and the development of techniques to improve biological function and devices to treat brain failure and other diseases, such as Parkinson's disease.^[24]

Massachusetts Institute of Technology (2014–present)

In December 2014, Collins moved to the Massachusetts Institute of Technology (MIT), where he was appointed the Termeer Professor of Medical Engineering & Science and was additionally named a professor at the Institute for Medical Engineering and Science.^[2] Since then, he has been a joint professor in the MIT Department of Biological Engineering and a faculty member of the Biophysics Program, the Synthetic Biology Center, Microbiology Graduate Program, Computational & Systems Biology Initiative, and Center for Microbiome Informatics & Therapeutics, all at MIT.^[14] He has also been a visiting professor of engineering science at the University of Oxford since 2023.^[14]

In 2016, Collins was appointed Allen Distinguished Investigator by the Allen Institute to research potential synthetic biology applications to antimicrobial resistance in drug-resistant bacteria.^[25][26] On October 3, 2018, he was named by Anantha Chandrakasan, the dean of the MIT School of Engineering, as faculty lead of the MIT Abdul Latif Jameel Clinic for Machine Learning in Health, alongside Regina Barzilay.^[27][28] In addition to the MIT Jameel Clinic, he leads the Antibiotics-AI Project at MIT, a research initiative which uses deep learning to discover new antibiotics.^[29] In 2024, he became a member of the Koch Institute for Integrative Cancer Research.^[14] He is currently a member of the editorial board of the scientific journals Science, Cell, and the Proceedings of the National Academy of Sciences.^[14]

Collins has been involved with a number of start-up companies, and his inventions and technologies have been licensed by over 25 biotech and medical device companies.^[30][31] He is the co-founder of the biomedical companies Senti Biosciences, Sherlock Biosciences, and Cellarity.^[14]

Harvard University

Collins has been a visiting professor of systems biology at Harvard Medical School since 2008.^[14] That same year, he became a founding Core Faculty Member of the Wyss Institute for Biologically Inspired Engineering, where he currently is lead of Living Cellular Devices.^[30] He has also been a member and senior associate^[32] of the Broad Institute of Harvard and MIT and a professor of the Harvard–MIT Program in Health Sciences and Technology since 2014.^[14]

Synthetic biology

Quick facts External videos ...

External videos
How we're using AI to discover new antibiotics, TedX (2020)
James Collins: Doing Good Science with an Underdog Spirit, Harvard Biotech (2026)

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Collins' work on synthetic gene circuits launched the field of synthetic biology.^[33] 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,^[34] 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. In the same issue of Nature, Elowitz and Leibler showed that one can build a synthetic genetic oscillator (called the repressilator) in E. coli.^[35] Collins’ Nature paper on the genetic toggle switch^[34] and Elowitz's and Leibler's Nature paper^[35] on the repressilator are considered landmark pieces which began the field of synthetic biology.^[33]

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,^[36] e.g., synthetic probiotics to serve as living diagnostics and living therapeutics to detect, treat and prevent infections such as cholera and C. difficile.^[37][38] He also designed and constructed engineered riboregulators (RNA switches) for sensing and control,^{[39][40][41][42][43][44]} microbial kill switches and genetic counters for biocontainment,^[45][46][47] synthetic bacteriophage to combat resistant bacterial infections,^[48][49] genetic switchboards for metabolic engineering,^[50] and tunable genetic switches for gene and cell therapy.^[51][52][53] 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),^{[54][55][56][57]} wearable biosensors,^[58] and portable biomolecular manufacturing (e.g., to produce vaccine antigens) in the developing world.^[59]

In the context of synthetic biology and regenerative medicine, Collins collaborated with Derrick Rossi and George Q. Daley on a study using synthetic mRNA technology for biomedical applications. The team showed that synthetic mRNA could be used for highly efficient stem cell reprogramming and redifferentiation. This work was published in Cell Stem Cell in 2010,^[60] and Rossi used this synthetic biology technology platform to found Moderna.^[61]

Collins has also used synthetic biology approaches (computational and experimental) to identify and address significant biological physics questions regarding the regulation of gene expression and cell dynamics. Collins, for example, has utilized synthetic gene networks to study the effects of positive feedback in genetic modules,^[62][63] the role and origin of stochastic fluctuations in eukaryotic gene expression,^[64] and the phenotypic consequences of gene expression noise and its effects on cell fate and microbial survival strategies in stressful environments.^[65] Importantly, Collins has also demonstrated how synthetic gene circuits can be used to test, validate and improve qualitative and quantitative models of gene regulation,^[66] and shown that biophysical theory and experiment can be coupled in bottom-up approaches to gain biological insights into the intricate processes of gene regulation.^[67]

Antibiotics and antibiotic resistance

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.^[68] Collins and collaborators showed that reverse-engineered gene networks can be used to identify drug targets, biological mediators and disease biomarkers.^[69]

Collins and collaborators discovered, using systems biology approaches, that all classes of bactericidal antibiotics induce a common oxidative damage cellular death pathway.^[70] This finding indicates that targeting bacterials systems that remediate oxidative damage, including the SOS DNA damage response, is a viable means of enhancing the effectiveness of all major classes of antibiotics and limiting the emergence of antibiotic resistance. 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.^[71]

Collins showed that certain metabolites could be used to enable bactericidal antibiotics to eradicate persistent, tolerant infections.^[72] 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.^[73] 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.^[74]

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.^[75] In 2020, Collins, Barzilay and the MIT Jameel Clinic were also awarded funding through The Audacious Project to create the Antibiotics-AI Project^[76] and expand on the discovery of halicin in using AI to respond to the antibiotic resistance crisis through the development of new classes of antibiotics.^[77]

Nonlinear dynamics in biological systems

Collins also pioneered the development and use of nonlinear dynamical approaches to study, mimic and improve biological function,^[78] expanding our ability to understand and harness the physics of living systems. Collins, for example, proposed that input noise could be used to enhance sensory function and motor control in humans.^[79][80] He and collaborators showed that touch sensation and balance control in young and older adults, patients with stroke, and patients with diabetic neuropathy could be improved with the application of sub-sensory mechanical noise,^[81] e.g., via vibrating insoles.^[82] 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.