Mark Brynildsen, AssociateProfessor,Dept. of Chemical and Biological Engineering at Princeton, will present: 

Addressing antibiotic resistance by understanding how antibiotics fail and searching for alternative treatments

ABSTRACTThe research of my group is motivated by the global public health threat of antibiotic resistance. Alarmingly, the increase in antibiotic-resistant infections has not been met by a comparable expansion to the antibiotic pipeline. Such a scenario has been recognized by the World Health Organization and countries around the world as a serious threat to our ability to treat bacterial infections. In my group, we seek to address this crisis by improving the efficacy of current antibiotics and identifying novel anti-infectives to complement conventional therapies. Specifically, in one area we examine why antibiotics fail to sterilize bacterial populations under best-case treatment scenarios: bacteria are sensitive to the antibiotic, the antibiotic concentration is well above that necessary to kill bacteria, and resistant mutants are not present in the population. This phenomenon is known as bacterial persistence, and it is thought to contribute to infection relapse following efficacious antibiotic treatment. Further, it is thought to provide a reservoir of bacteria from which resistant mutants can arise during chronic infections. Our work on bacterial persistence centers on understanding the physiological aspects of persisters that allow them to survive when their genetically identical kin cannot. In our other area, we apply principles and techniques from metabolic engineering to understand how bacteria defend themselves against immune antimicrobials, such as nitric oxide and hydrogen peroxide. Notably, sensitization of pathogens to immune effectors constitutes an anti-infective approach that could produce treatments that are orthogonal to current antibiotics, and thus able to restock the antibiotic medicine chest. In this talk, I will summarize our work in these areas and discuss how the knowledge we have uncovered can contribute to the fight against antibiotic resistance.

BIO:      Dr. Mark P. Brynildsen received his B.S. in Chemical Engineering from Rutgers University, New Brunswick in 2002 and earned his Ph.D. in Chemical Engineering from the University of California, Los Angeles (UCLA) in 2008, where he worked with Dr. James C. Liao. After working for 2 years as a Howard Hughes Medical Institute (HHMI) post-doctoral associate with James J. Collins within the Department of Biomedical Engineering at Boston University, Mark joined the faculty of the Department of Chemical and Biological Engineering at Princeton University in 2010. Currently, he holds the position of Associate Professor of Chemical and Biological Engineering at Princeton and is the Director of Undergraduate Studies. The overarching goal of his research group is to improve the performance of current antibiotics and identify targets for novel anti-infectives. To accomplish this, the Brynildsen group uses computational and experimental techniques in systems biology and metabolic engineering to develop novel, fundamental understanding of the molecular mechanisms and networks pathogens use to thwart immune antimicrobials and antibiotics. Mark’s research has been published in journals such as Nature, Nature Biotechnology, Nature Communications, PNAS, Molecular Cell, and Current Biology, and he has been the recipient of a Howard B. Wentz, Jr. Junior Faculty Award and an NSF CAREER Award.

Mark Brynildsen, AssociateProfessor,Dept. of Chemical and Biological Engineering at Princeton, will present: 

Addressing antibiotic resistance by understanding how antibiotics fail and searching for alternative treatments

ABSTRACTThe research of my group is motivated by the global public health threat of antibiotic resistance. Alarmingly, the increase in antibiotic-resistant infections has not been met by a comparable expansion to the antibiotic pipeline. Such a scenario has been recognized by the World Health Organization and countries around the world as a serious threat to our ability to treat bacterial infections. In my group, we seek to address this crisis by improving the efficacy of current antibiotics and identifying novel anti-infectives to complement conventional therapies. Specifically, in one area we examine why antibiotics fail to sterilize bacterial populations under best-case treatment scenarios: bacteria are sensitive to the antibiotic, the antibiotic concentration is well above that necessary to kill bacteria, and resistant mutants are not present in the population. This phenomenon is known as bacterial persistence, and it is thought to contribute to infection relapse following efficacious antibiotic treatment. Further, it is thought to provide a reservoir of bacteria from which resistant mutants can arise during chronic infections. Our work on bacterial persistence centers on understanding the physiological aspects of persisters that allow them to survive when their genetically identical kin cannot. In our other area, we apply principles and techniques from metabolic engineering to understand how bacteria defend themselves against immune antimicrobials, such as nitric oxide and hydrogen peroxide. Notably, sensitization of pathogens to immune effectors constitutes an anti-infective approach that could produce treatments that are orthogonal to current antibiotics, and thus able to restock the antibiotic medicine chest. In this talk, I will summarize our work in these areas and discuss how the knowledge we have uncovered can contribute to the fight against antibiotic resistance.

BIO:      Dr. Mark P. Brynildsen received his B.S. in Chemical Engineering from Rutgers University, New Brunswick in 2002 and earned his Ph.D. in Chemical Engineering from the University of California, Los Angeles (UCLA) in 2008, where he worked with Dr. James C. Liao. After working for 2 years as a Howard Hughes Medical Institute (HHMI) post-doctoral associate with James J. Collins within the Department of Biomedical Engineering at Boston University, Mark joined the faculty of the Department of Chemical and Biological Engineering at Princeton University in 2010. Currently, he holds the position of Associate Professor of Chemical and Biological Engineering at Princeton and is the Director of Undergraduate Studies. The overarching goal of his research group is to improve the performance of current antibiotics and identify targets for novel anti-infectives. To accomplish this, the Brynildsen group uses computational and experimental techniques in systems biology and metabolic engineering to develop novel, fundamental understanding of the molecular mechanisms and networks pathogens use to thwart immune antimicrobials and antibiotics. Mark’s research has been published in journals such as Nature, Nature Biotechnology, Nature Communications, PNAS, Molecular Cell, and Current Biology, and he has been the recipient of a Howard B. Wentz, Jr. Junior Faculty Award and an NSF CAREER Award.