James Collins (Boston University) - Work

Work

Collins has pioneered the development and use of nonlinear dynamical approaches to study, mimic and improve biological function, and helped to transform biology into an engineering science. His current research interests include: synthetic biology - modeling, designing and constructing synthetic gene networks, and systems biology - reverse engineering naturally occurring gene regulatory networks.

Collins has invented a number of novel devices and techniques, including vibrating insoles for enhancing balance, a prokaryotic riboregulator, bistable genetic toggle switches for biotechnology and bioenergy applications, dynamical control techniques for eliminating cardiac arrhythmias, and systems biology techniques for identifying drug targets and disease mediators.

Collins proposed that input noise could be used to enhance sensory function and motor control in humans. 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, e.g., via vibrating insoles. 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.

Collins has pioneered the use of techniques from nonlinear dynamics and molecular biology to model, design and construct engineered gene networks, leading to the development of the field of synthetic biology. Collins and collaborators have created genetic toggle switches, RNA switches, genetic counters, programmable cells, tunable mammalian genetic switches, and engineered bacteriophage, each with broad applications in biotechnology and biomedicine.

Collins is also one of the leading researchers in systems biology, pioneering the use of experimental-computational biophysical techniques to reverse engineer and analyze endogenous gene regulatory networks. Collins and collaborators showed that reverse-engineered gene networks can be used to identify drug targets, biological mediators and disease biomarkers.

Collins and collaborators discovered, using systems biology approaches, that all classes of bactericidal antibiotics induce a common oxidative damage cellular death pathway. 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. Collins and co-workers also discovered that sublethal levels of antibiotics activate mutagenesis by stimulating the production of reactive oxygen species, leading to multidrug resistance. This discovery has important implications for the widespread use and misuse of antibiotics. Recently, Collins and colleagues, using their systems approaches, 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.