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James J. Collins

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James J. Collins
Born (1965-06-26) June 26, 1965 (age 59)
New York City, U.S.
EducationCollege of the Holy Cross (BA)
University of Oxford (DPhil)
Known forSynthetic biology,
Discovery of halicin and abaucin
Spouse
Mary McNaughton Collins
​
​
(m. 1990)​
AwardsMacArthur Fellowship (2003)
NIH Director's Pioneer Award (2007)
Lagrange Prize (2010)
HFSP Nakasone Award (2015)
Gabbay Award (2017)
Dickson Prize in Medicine (2020)
Max Delbruck Prize (2020)
Feynman Prize (2023)
Clarivate Citation Laureate (2023)
Scientific career
FieldsBiological engineering
Biomedical engineering
Systems biology
Synthetic biology
InstitutionsMassachusetts Institute of Technology
Harvard University
Boston University
Ragon Institute
Wyss Institute
Broad Institute
ThesisJoint Mechanics: Modeling of the Lower Limb (1990)
Doctoral advisorJohn O’Connor

James Joseph Collins (born June 26, 1965) is an American biomedical engineer and bioengineer who serves as the Termeer Professor of Medical Engineering & Science at the Massachusetts Institute of Technology (MIT), where he is also a director at the MIT Abdul Latif Jameel Clinic for Machine Learning in Health.

Collins conducted research showing that artificial intelligence (AI) approaches can be used to discover novel antibiotics, such as halicin and abaucin.[1] He serves as the Director of the Antibiotics-AI Project at MIT, which is supported by The Audacious Project, and is a member of the Harvard–MIT Program in Health Sciences and Technology. He is also a core faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard University and a member of the Broad Institute.[2]

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.[3]

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. In 2023, he was awarded a Clarivate Citation for research most likely to receive a Nobel Prize.

Early life and education

[edit]

Collins was born on June 26, 1965, in The Bronx, then moved to Bellerose, New York.[4] His father was an aviation engineer who worked on projects for NASA and the military.[5] At age 10, Collins moved to New Hampshire with his family after finishing elementary school,[6] growing up in Nashua.[7] He first developed an interest in medical engineering when one of his grandfathers became blind and the other suffered multiple strokes.[5]

Collins originally intended to study electrical engineering as an undergraduate and was accepted to the Massachusetts Institute of Technology (MIT) and the Rensselaer Polytechnic Institute (RPI) but decided instead to attend the College of the Holy Cross, finding the atmosphere at the college more friendly. Collins later recalled, "I fell in love with the place. I wanted to work hard and get a strong education, but I also wanted to enjoy myself. I wanted to get a broad experience, and I felt I could get that at Holy Cross".[3]

At Holy Cross, Collins was a class officer and a member of the track and cross country teams, where he was a 4:17 miler.[8] He also wrote for the school newspaper and taught as part of the Confraternity of Christian Doctrine (CCD). As an undergraduate, he had been awarded a President's Volunteer Service Award and was designated as a Fenwick Scholar in 1986, one of the college's highest honors.[9] Collins graduated from Holy Cross in 1987 as class valedictorian, receiving a Bachelor of Arts (BA) in physics, summa cum laude.[3] His undergraduate thesis was titled "Functional Neuromuscular Stimulation: An Analysis of the Biomechanical and Neuromuscular Foundations of Walking".[10]

After graduating from Holy Cross, Collins was one of four students from New England to be selected for a Rhodes Scholarship, which he used to study medical engineering in England at Oxford University.[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.[12] His dissertation was titled "Joint Mechanics: Modelling of the Lower Limb" and was supervised by John J. O'Connor.[13]

Career

[edit]

Collins returned to the United States to join the faculty of Boston University. There, he established a laboratory and became the university's William F. Warren Distinguished Professor, a University Professor, a professor of biomedical engineering, a professor of medicine, and co-director of the Center for BioDynamics and Director of the Center of Synthetic Biology. In 2008, Collins was named as a Howard Hughes Medical Institute investigator, becoming the first investigator from Boston University.[7]

In 2014, Collins moved to become a professor at the Massachusetts Institute of Technology.[14] 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.[15][16]

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.

In 2010, Collins was appointed by President Barack Obama to be a member of the Presidential Commission for the Study of Bioethical Issues.[17]

Work

[edit]

Synthetic biology

[edit]

Collins' work on synthetic gene circuits launched the field of synthetic biology.[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. In the same issue of Nature, Elowitz and Leibler showed that one can build a synthetic genetic oscillator (called the repressilator) in E. coli.[20] Collins’ Nature paper on the genetic toggle switch[19] and Elowitz's and Leibler's Nature paper[20] on the repressilator are considered landmark pieces, ones that marks the beginnings of synthetic biology.[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. difficile.[22][23] He also designed and constructed engineered riboregulators (RNA switches) for sensing and control,[24][25][26][27][28][29] microbial kill switches and genetic counters for biocontainment,[30][31][32] synthetic bacteriophage to combat resistant bacterial infections,[33][34] genetic switchboards for metabolic engineering,[35] and tunable genetic switches for gene and cell therapy.[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.[44]

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,[45] and Rossi used this synthetic biology technology platform to found Moderna.[46]

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,[47][48] the role and origin of stochastic fluctuations in eukaryotic gene expression,[49] and the phenotypic consequences of gene expression noise and its effects on cell fate and microbial survival strategies in stressful environments.[50] Importantly, Collins has also demonstrated how synthetic gene circuits can be used to test, validate and improve qualitative and quantitative models of gene regulation,[51] 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.[52]

Antibiotics and antibiotic resistance

[edit]

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.[55] 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.[56]

Collins showed that certain metabolites could be used to enable bactericidal antibiotics to eradicate persistent, tolerant infections.[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.[60] 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.[61]

Nonlinear dynamics in biological systems

[edit]

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. Collins, for example, proposed that input noise could be used to enhance sensory function and motor control in humans.[63][64] 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,[65] e.g., via vibrating insoles.[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.

Awards

[edit]

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[67] – and the Scientific American 50 – the top 50 outstanding leaders in science and technology.[68]

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",[69] becoming the first bioengineer to receive this honor.[70] 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.[71] 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.[72]

In 2023, Collins was named a Clarivate Citation Laureate along with Michael Elowitz and Stanislas Leibler "for pioneering work on synthetic gene circuits, which launched the field of synthetic biology".[73]

Personal life

[edit]

Collins' wife is Mary McNaughton Collins; they met while undergraduates at Holy Cross and married in 1990. She is a professor at Harvard Medical School and a physician at Massachusetts General Hospital.[3] They have two children: Katie, a Marshall Scholar at the University of Cambridge, and Danny, a Knight-Hennessy Scholar at Stanford University.[74][75]

References

[edit]
  1. ^ Trafton, Anne (December 20, 2023). "Using AI, MIT researchers identify a new class of antibiotic candidates". MIT News. Massachusetts Institute of Technology. Retrieved May 6, 2024.
  2. ^ Saunders, Fenella (February 6, 2023). "Synthesizing Engineering and Biology". American Scientist. Sigma Xi. Retrieved December 19, 2023.
  3. ^ a b c d Reardon, Michael (Winter 2007). "The Profile: James J. Collins Jr. '87". Holy Cross Magazine. Vol. 41, no. 1. College of the Holy Cross. p. 80. Archived from the original on August 22, 2016. Retrieved April 15, 2007.
  4. ^ Khan, Firdos Alam (May 8, 2014). Biotechnology in Medical Sciences. CRC Press. ISBN 978-1-4822-2367-5.
  5. ^ a b Trafton, Anne (November 14, 2015). "Reprogramming biology: Biological engineer James Collins designs genetic circuits with novel functions". MIT News. Massachusetts Institute of Technology. Retrieved December 19, 2023.
  6. ^ "James Collins, Ph.D. | AIMBE College of Fellows Class of 2000". American Institute for Medical and Biological Engineering. Retrieved December 19, 2023 – via Xconomy.
  7. ^ a b Baker, Billy (November 24, 2008). "Dream gig grants him freedom to explore". The Boston Globe. p. 16. Retrieved December 20, 2023.
  8. ^ Zaman, Muhammed (April 20, 2020). Biography of Resistance. Harper. ISBN 978-0062862976.
  9. ^ Brady 2012, p. 184.
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  26. ^ Green AA, Kim J, Ma D, Silver PA, Collins JJ, Yin P (2017). "Complex cellular logic computation using ribocomputing devices". Nature. 548 (7665): 117–121. Bibcode:2017Natur.548..117G. doi:10.1038/nature23271. PMC 6078203. PMID 28746304.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ^ Angenent-Mari NM, Garruss AS, Soenksen LR, Church G, Collins JJ (2020). "A deep learning approach to programmable RNA switches". Nat Commun. 11 (1): 5057. Bibcode:2020NatCo..11.5057A. doi:10.1038/s41467-020-18677-1. PMC 7541447. PMID 33028812.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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  30. ^ Friedland AE, Lu TK, Wang X, Shi D, Church G, Collins JJ (2009). "Synthetic gene networks that count". Science. 324 (5931): 1199–202. Bibcode:2009Sci...324.1199F. doi:10.1126/science.1172005. PMC 2690711. PMID 19478183.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  31. ^ Callura JM, Dwyer DJ, Isaacs FJ, Cantor CR, Collins JJ (2010). "Tracking, tuning, and terminating microbial physiology using synthetic riboregulators". Proc Natl Acad Sci U S A. 107 (36): 15898–903. Bibcode:2010PNAS..10715898C. doi:10.1073/pnas.1009747107. PMC 2936621. PMID 20713708.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  32. ^ Chan CT, Lee JW, Cameron DE, Bashor CJ, Collins JJ (2016). "'Deadman' and 'Passcode' microbial kill switches for bacterial containment". Nat Chem Biol. 12 (2): 82–6. doi:10.1038/nchembio.1979. PMC 4718764. PMID 26641934.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  33. ^ Lu TK, Collins JJ (2007). "Dispersing biofilms with engineered enzymatic bacteriophage". Proc Natl Acad Sci U S A. 104 (27): 11197–202. Bibcode:2007PNAS..10411197L. doi:10.1073/pnas.0704624104. PMC 1899193. PMID 17592147.
  34. ^ Lu TK, Collins JJ (2009). "Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy". Proc Natl Acad Sci U S A. 106 (12): 4629–34. Bibcode:2009PNAS..106.4629L. doi:10.1073/pnas.0800442106. PMC 2649960. PMID 19255432.
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  36. ^ Deans TL, Cantor CR, Collins JJ (2007). "A tunable genetic switch based on RNAi and repressor proteins for regulating gene expression in mammalian cells". Cell. 130 (2): 363–72. doi:10.1016/j.cell.2007.05.045. PMID 17662949. S2CID 7960766.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  37. ^ Cho JH, Collins JJ, Wong WW (2018). "Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses". Cell. 173 (6): 1426–1438.e11. doi:10.1016/j.cell.2018.03.038. PMC 5984158. PMID 29706540.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  38. ^ Cho JH, Okuma A, Sofjan K, Lee S, Collins JJ, Wong WW (2021). "Engineering advanced logic and distributed computing in human CAR immune cells". Nat Commun. 12 (1): 792. Bibcode:2021NatCo..12..792C. doi:10.1038/s41467-021-21078-7. PMC 7862674. PMID 33542232.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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  54. ^ Gardner, TS; di Bernardo D; Lorenz D; Collins JJ (July 4, 2003). "Inferring genetic networks and identifying compound of action via expression profiling". Science. 301 (5629): 102–105. doi:10.1126/science.1081900. PMID 12843395. S2CID 8356492.
  55. ^ Kohanski, MA; Dwyer DJ; Hayete B; Lawrence CA; Collins JJ. (2007). "A common mechanism of cellular death induced by bactericidal antibiotics". Cell. 130 (5): 797–810. doi:10.1016/j.cell.2007.06.049. PMID 17803904. S2CID 1103795.
  56. ^ Kohanski MA, Dwyer DJ, Wierzbowski J, Cottarel G, Collins JJ (2008). "Mistranslation of membrane proteins and two-component system activation trigger antibiotic-mediated cell death". Cell. 135 (4): 679–90. doi:10.1016/j.cell.2008.09.038. PMC 2684502. PMID 19013277.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  57. ^ Allison KR, Brynildsen MP, Collins JJ (2011). "Metabolite-enabled eradication of bacterial persisters by aminoglycosides". Nature. 473 (7346): 216–20. Bibcode:2011Natur.473..216A. doi:10.1038/nature10069. PMC 3145328. PMID 21562562.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  58. ^ Kohanski, MA; DePristo MA; Collins JJ. (2010). "Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis". Molecular Cell. 37 (3): 311–320. doi:10.1016/j.molcel.2010.01.003. PMC 2840266. PMID 20159551.
  59. ^ Lee, HH; Molla MN; Cantor CR; Collins JJ. (2010). "Bacterial charity work leads to population-wide resistance". Nature. 467 (7311): 82–85. Bibcode:2010Natur.467...82L. doi:10.1038/nature09354. PMC 2936489. PMID 20811456.
  60. ^ Stokes, Jonathan M.; Yang, Kevin; Swanson, Kyle; Jin, Wengong; Cubillos-Ruiz, Andres; Donghia, Nina M.; MacNair, Craig R.; French, Shawn; Carfrae, Lindsey A.; Bloom-Ackermann, Zohar; Tran, Victoria M. (February 20, 2020). "A Deep Learning Approach to Antibiotic Discovery". Cell. 180 (4): 688–702.e13. doi:10.1016/j.cell.2020.01.021. ISSN 1097-4172. PMC 8349178. PMID 32084340.
  61. ^ "Jim Collins receives funding to harness AI for drug discovery". MIT News | Massachusetts Institute of Technology. April 23, 2020. Retrieved November 13, 2020.
  62. ^ Collins JJ (1994). "Random walking during quiet standing". Phys Rev Lett. 73 (5): 764–767. Bibcode:1994PhRvL..73..764C. doi:10.1103/PhysRevLett.73.764. PMID 10057531.
  63. ^ Collins JJ, Chow CC, Imhoff TT (1995). "Stochastic resonance without tuning". Nature. 376 (6537): 236–8. Bibcode:1995Natur.376..236C. doi:10.1038/376236a0. PMID 7617033. S2CID 4314968.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  64. ^ Collins JJ, Imhoff TT, Grigg P (1996). "Noise-enhanced information transmission in rat SA1 cutaneous mechanoreceptors via aperiodic stochastic resonance". J Neurophysiol. 76 (1): 642–5. doi:10.1152/jn.1996.76.1.642. PMID 8836253.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  65. ^ Collins JJ, Imhoff TT, Grigg P (1996). "Noise-enhanced tactile sensation". Nature. 383 (6603): 770. Bibcode:1996Natur.383..770C. doi:10.1038/383770a0. PMID 8893000. S2CID 3660648.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  66. ^ Priplata, A; Niemi J; Harry J; Lipsitz LA; Collins JJ (October 4, 2003). "Vibrating insoles and balance control in elderly people". The Lancet. 362 (9390): 1123–1124. doi:10.1016/S0140-6736(03)14470-4. PMID 14550702. S2CID 33216209.
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  69. ^ "MacArthur Fellows, October 2003". John D. and Catherine T. MacArthur Foundation. Archived from the original on October 16, 2007. Retrieved April 15, 2007.
  70. ^ Tucker, Ian (May 21, 2011). "James Collins: A spoonful of sugar helps the medicine go down". The Guardian. ISSN 0261-3077. Retrieved April 22, 2024.
  71. ^ Shaner, Karen (April 13, 2016). "James Collins appointed 2016 Allen Distinguished Investigator". MIT News. Massachusetts Institute of Technology. Retrieved December 19, 2023.
  72. ^ Brick, Tricia (Spring 2006). "Genius at Work". Bostonia. pp. 20–25. Archived from the original on October 19, 2012. Retrieved June 12, 2009.
  73. ^ "James J. Collins named a Citation Laureate". Harvard-MIT Health Sciences and Technology. September 22, 2023. Retrieved December 19, 2023.
  74. ^ "Healthcare and Life Sciences: James Collins". Irish America. October 5, 2022. Retrieved December 19, 2023.
  75. ^ "Duke Senior Launches Himself Towards Big Regwards". Duke Today. October 19, 2023. Archived from the original on June 25, 2020. Retrieved September 29, 2024.

Additional references

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