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Mark Brynildsen

Mark P. Brynildsen

Assistant Professor in Chemical and Biological Engineering

B.S., Rutgers University, 2002
Ph.D., University of California, Los Angeles, 2008
HHMI Postdoctoral Associate, Boston University, 2008-2010

Room: 205 Hoyt Laboratory
Phone: 609-258-1995
Email: mbrynild@princeton.edu

Webpage: Brynildsen Research Group

Honors and Awards

  • Howard B. Wentz, Jr. Junior Faculty Award, 2015
  • NSF CAREER Award, 2015-2020
  • UCLA Dissertation Year Fellowship, 2007-08
  • UCLA Quality of Graduate Education Stipend, 2006
  • Arco Graduate Student Fellowship, 2006
  • California NanoSystems Institute (CNSI) Graduate Student Fellowship, 2002-03

Publications

Research Areas

Research Interests

With the ever-increasing incidence of antibiotic-resistant infections and a weak pipeline of new antibiotics, our antibiotic arsenal is in danger of becoming obsolete. Since conventional antibiotic discovery is failing to keep pace with the rise of resistance, fresh perspectives and novel methodologies are needed to address this critical public health issue. The main focus of our group is to use both computational and experimental techniques in systems biology, synthetic biology, and metabolic engineering to understand and combat infectious disease. We focus on two key areas: host-pathogen interactions and bacterial persistence toward antibiotics.

Host-pathogen interactions: The increase in the frequency of antibiotic-resistant strains has researchers searching for new antimicrobials or novel ways to potentiate current therapeutics. One exciting approach with great potential is antivirulence therapy, which focuses on disrupting the ability of a pathogen to infect a host. Rather than targeting essential bacterial functions as current antibiotics do, antivirulence therapy targets essential host-pathogen interactions required for infection such as adhesion, quorum sensing, and susceptibility to immune attack. These therapies are less prone to resistance development due to their ability to provide selective pressure only within the host, and have the potential to greatly expand our antibacterial capabilities. In this area, we leverage our knowledge and understanding of bacterial metabolism and stress responses to increase the susceptibility of pathogens to killing by various immune antimicrobials, including reactive oxygen species and reactive nitrogen species.

Bacterial persistence: Bacterial persistence is a non-genetic, non-inherited (epigenetic) ability in bacteria to tolerate antibiotics and other stress. This distinct physiological state is thought to cause chronic and recurrent infection, and represents an insurance policy in which a small portion of cells enter dormancy and sacrifice their ability to replicate in order to survive stress at a future time. The proportion of persisters in a population varies by strain and environment (generally 1 in 100 to 1 in 1,000,000 cells), and the mechanism of persister formation as well as the content of their physiology remain elusive. A major goal of our group is the reconstruction of persister physiology using systems biology to identify active portions of their metabolic, signal transduction, and transcriptional regulatory networks. This work will provide network-level knowledge of the phenotype and direct efforts to eliminate persisters as a source of chronic infection.