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
Webpage: Brynildsen Research Group
Honors and Awards
- 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
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 three key areas: host-pathogen interactions, bacterial persistence, and biofilms.
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 antimicrobial capabilities. In this area, we employ tools from systems biology, synthetic biology, and metabolic engineering to understand and increase the susceptibility of pathogens to killing by various immune antimicrobials, including reactive oxygen species, reactive nitrogen species, and antimicrobial peptides.
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 10-2 to 10-5), 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 the first cellular-level persister network and direct efforts to eliminate persisters as a source of chronic infection.
Biofilms: Biofilms are communities of bacterial cells embedded in a self-generated extracellular polymer matrix (EPM) that protects them from exogenous stress. The pathogenicities of a number of organisms including Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus, and uropathogenic Escherichia coli have been linked to biofilm formation. Most research in this area has focused on the genetics, signaling events, and surface modifications that affect initial adhesion or biofilm maturation. Interestingly, despite the fact that EPM is a metabolic product of bacteria, little research has focused on how to metabolically impair an organism’s ability to synthesize EPM. Our group uses metabolic engineering techniques employed for metabolic optimization to identify strategies that minimize the production or negatively impact the integrity of biofilms (e.g., suboptimal composition). This work will lay the foundation for a novel class of antibiofilm therapies based on biosynthetic limitation.