James Collins (bioengineer)

James Joseph Collins (born June 26, 1965) is an American bioengineer who serves as the Termeer Professor of Medical Engineering & Science at the Massachusetts Institute of Technology (MIT). Collins conducted research showing that artificial intelligence (AI) approaches can be used to discover novel antibiotics, such as halicin and abaucin. He serves as the Director of the Antibiotics-AI Project at MIT, which is supported by The Audacious Project, and is the faculty lead for life sciences at the MIT Jameel Clinic.

For other people named James Collins, see James Collins (disambiguation).

James Collins
Born
James Joseph Collins

(1965-06-26) June 26, 1965
New York City, New York, U.S.
Alma materCollege of the Holy Cross (BA)
Balliol College, Oxford (DPhil)
Known forSynthetic biology; discovery of halicin and abaucin
AwardsDickson Prize in Medicine
HFSP Nakasone Award
Max Delbruck Prize
Gabbay Award
MacArthur Fellow
National Academy of Sciences
National Academy of Engineering
National Academy of Medicine
American Academy of Arts & Sciences
Scientific career
FieldsBioengineering
Medical engineering
InstitutionsMassachusetts Institute of Technology
Harvard University
Boston University
ThesisJoint Mechanics: Modeling of the Lower Limb (1990)
Doctoral advisorJohn O’Connor

Collins is one of the founders of the field of synthetic biology, and his work on synthetic gene circuits and programmable cells has led to the development of new classes of diagnostics and therapeutics, which have influenced research in detecting and treating infections caused by emerging pathogens such as Ebola, Zika, SARS-CoV-2, and antibiotic-resistant bacteria. He is also a researcher in systems biology, having made discoveries regarding the actions of antibiotics and the emergence of antibiotic resistance.[1]

Collins is a member of the National Academy of Engineering, the National Academy of Medicine, and the National Academy of Sciences, for his contributions to synthetic biology and engineered gene networks.

Biography

Collins received a B.A. in physics, summa cum laude, from the College of the Holy Cross in 1987 as class valedictorian. He was awarded a Rhodes Scholarship to study medical engineering at the Balliol College, Oxford, where he earned a DPhil in 1990.[2] Currently, Collins is the Termeer Professor of Medical Engineering & Science and Professor of Biological Engineering at MIT. Collins is also a core founding faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University and a member of the Broad Institute. Collins is also faculty lead for life sciences at the MIT Jameel Clinic since 2018.[3][4]

From 1990 to 2014, he was on the faculty at Boston University, where he was a William F. Warren Distinguished Professor, a University Professor, Professor of Biomedical Engineering, Professor of Medicine, and co-director of the Center for BioDynamics and Director of the Center of Synthetic Biology.

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. Collins is the scientific co-founder of several biotech companies and non-profit organizations.

Collins ran track and cross country at Holy Cross (he was a 4:17 miler), and earned a blue playing for the varsity basketball team at the University of Oxford.

Work

Synthetic biology

Collins' work on synthetic gene circuits launched the field of synthetic biology.[5] 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,[6] 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.[7] Collins’ Nature paper on the genetic toggle switch[6] and Elowitz's and Leibler's Nature paper[7] on the repressilator are considered landmark pieces, ones that marks the beginnings of synthetic biology.[5]

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,[8] e.g., synthetic probiotics to serve as living diagnostics and living therapeutics to detect, treat and prevent infections such as cholera and C. difficile.[9][10] He also designed and constructed engineered riboregulators (RNA switches) for sensing and control,[11][12][13][14][15][16] microbial kill switches and genetic counters for biocontainment,[17][18][19] synthetic bacteriophage to combat resistant bacterial infections,[20][21] genetic switchboards for metabolic engineering,[22] and tunable genetic switches for gene and cell therapy.[23][24][25] 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),[26][27][28][29] wearable biosensors,[30] and portable biomolecular manufacturing (e.g., to produce vaccine antigens) in the developing world.[31]

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,[32] and Rossi used this synthetic biology technology platform to found Moderna.[33]

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,[34][35] the role and origin of stochastic fluctuations in eukaryotic gene expression,[36] and the phenotypic consequences of gene expression noise and its effects on cell fate and microbial survival strategies in stressful environments.[37] Importantly, Collins has also demonstrated how synthetic gene circuits can be used to test, validate and improve qualitative and quantitative models of gene regulation,[38] 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.[39]

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.[40][41][42][43] Collins and collaborators showed that reverse-engineered gene networks can be used to identify drug targets, biological mediators and disease biomarkers.[44][45][46]

Collins and collaborators discovered, using systems biology approaches, that all classes of bactericidal antibiotics induce a common oxidative damage cellular death pathway.[47] 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.[48][49][50][51][52][53]

Collins showed that certain metabolites could be used to enable bactericidal antibiotics to eradicate persistent, tolerant infections.[54][55][56] 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.[57] 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.[58]

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.[59][60][61] In 2020, Collins, Barzilay and the MIT Jameel Clinic were also awarded funding through The Audacious Project to create the Antibiotics-AI Project 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.[62]

Nonlinear dynamics in biological systems

Collins also pioneered the development and use of nonlinear dynamical approaches to study, mimic and improve biological function,[63][64][65] 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.[66][67] 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,[68][69][70][71] e.g., via vibrating insoles.[72] 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.

Awards

Collins' scientific accomplishments have been recognized by numerous awards, including the Dickson Prize in Medicine, the Sanofi-Institut Pasteur Award, the HFSP Nakasone Award, the Max Delbruck Prize, the Gabbay Award, the NIH Director's Pioneer Award, the Ellison Medical Foundation Senior Scholar Award in Aging, the inaugural Anthony J. Drexel Exceptional Achievement Award, the Lagrange Prize from the CRT Foundation in Italy, the BMES Robert A. Pritzker Award, the Promega Biotechnology Research Award, and being selected for Technology Review's inaugural TR100 100 young innovators who will shape the future of technology[73] – and the Scientific American 50 – the top 50 outstanding leaders in science and technology.[74]

Collins is a Fellow of the American Physical Society, the Institute of Physics, and the American Institute for Medical and Biological Engineering. In 2003, he received a MacArthur Foundation "Genius Award",[75] becoming the first bioengineer to receive this honor. Collins' award citation noted, "Throughout his research, Collins demonstrates a proclivity for identifying abstract principles that underlie complex biological phenomena and for using these concepts to solve concrete, practical problems.". He was also honored as a Medical All-Star by the Boston Red Sox, and threw out the first pitch at a Red Sox game in Fenway Park. In 2016, Collins was named an Allen Distinguished Investigator by the Paul G. Allen Frontiers Group. Collins is an elected member of all three U.S. national academies – the National Academy of Sciences, the National Academy of Engineering, and the National Academy of Medicine. He is also an elected fellow of the American Academy of Arts and Sciences, as well as a charter fellow of the National Academy of Inventors.

Collins has received teaching awards at Boston University, including the Biomedical Engineering Teacher of the Year Award, the College of Engineering Professor of the Year Award, and the Metcalf Cup and Prize for Excellence in Teaching, which is the highest teaching honor awarded by Boston University.[76]

References
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