Kathryn Brink is a postdoctoral scholar in the Center for International Security and Cooperation (CISAC), where she works with Megan Palmer and David Relman. Kathryn is a synthetic biologist by training. During her PhD, Kathryn studied bacterial two-component systems (TCSs), signal transduction pathways that bacteria use to sense and respond to changes in their environment. TCSs play important roles in host-pathogen interactions and can be engineered for medical and environmental biosensing applications. In her thesis work, Kathryn developed engineering and screening approaches to discover and characterize the stimuli that activate these pathways.
At CISAC, Kathryn's research focuses on risk management and assessment in biological science and engineering, with the goals of improving the governance of biological research and reducing the risk of its misuse. She investigates factors associated with attention to risk among scientists and engineers and studies risk assessment processes in the life sciences.
PhD, Rice University, Systems, Synthetic, and Physical Biology (2021)
BS, Massachusetts Institute of Technology, Biological Engineering (2016)
David Relman, Postdoctoral Faculty Sponsor
Guiding Ethical Principles in Engineering Biology Research.
ACS synthetic biology
Engineering biology is being applied toward solving or mitigating some of the greatest challenges facing society. As with many other rapidly advancing technologies, the development of these powerful tools must be considered in the context of ethical uses for personal, societal, and/or environmental advancement. Researchers have a responsibility to consider the diverse outcomes that may result from the knowledge and innovation they contribute to the field. Together, we developed a Statement of Ethics in Engineering Biology Research to guide researchers as they incorporate the consideration of long-term ethical implications of their work into every phase of the research lifecycle. Herein, we present and contextualize this Statement of Ethics and its six guiding principles. Our goal is to facilitate ongoing reflection and collaboration among technical researchers, social scientists, policy makers, and other stakeholders to support best outcomes in engineering biology innovation and development.
View details for DOI 10.1021/acssynbio.1c00129
View details for PubMedID 33977723
Mucosal acidosis elicits a unique molecular signature in epithelia and intestinal tissue mediated by GPR31-induced CREB phosphorylation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2021; 118 (20)
Metabolic changes associated with tissue inflammation result in significant extracellular acidosis (EA). Within mucosal tissues, intestinal epithelial cells (IEC) have evolved adaptive strategies to cope with EA through the up-regulation of SLC26A3 to promote pH homeostasis. We hypothesized that EA significantly alters IEC gene expression as an adaptive mechanism to counteract inflammation. Using an unbiased RNA sequencing approach, we defined the impact of EA on IEC gene expression to define molecular mechanisms by which IEC respond to EA. This approach identified a unique gene signature enriched in cyclic AMP response element-binding protein (CREB)-regulated gene targets. Utilizing loss- and gain-of-function approaches in cultured epithelia and murine colonoids, we demonstrate that EA elicits prominent CREB phosphorylation through cyclic AMP-independent mechanisms that requires elements of the mitogen-activated protein kinase signaling pathway. Further analysis revealed that EA signals through the G protein-coupled receptor GPR31 to promote induction of FosB, NR4A1, and DUSP1. These studies were extended to an in vivo murine model in conjunction with colonization of a pH reporter Escherichia coli strain that demonstrated significant mucosal acidification in the TNFΔARE model of murine ileitis. Herein, we observed a strong correlation between the expression of acidosis-associated genes with bacterial reporter sfGFP intensity in the distal ileum. Finally, the expression of this unique EA-associated gene signature was increased during active inflammation in patients with Crohn's disease but not in the patient control samples. These findings establish a mechanism for EA-induced signals during inflammation-associated acidosis in both murine and human ileitis.
View details for DOI 10.1073/pnas.2023871118
View details for Web of Science ID 000656222000002
View details for PubMedID 33972436
View details for PubMedCentralID PMC8157950
Rewiring bacterial two-component systems by modular DNA-binding domain swapping
NATURE CHEMICAL BIOLOGY
2019; 15 (7): 690-+
Two-component systems (TCSs) are the largest family of multi-step signal transduction pathways and valuable sensors for synthetic biology. However, most TCSs remain uncharacterized or difficult to harness for applications. Major challenges are that many TCS output promoters are unknown, subject to cross-regulation, or silent in heterologous hosts. Here, we demonstrate that the two largest families of response regulator DNA-binding domains can be interchanged with remarkable flexibility, enabling the corresponding TCSs to be rewired to synthetic output promoters. We exploit this plasticity to eliminate cross-regulation, un-silence a gram-negative TCS in a gram-positive host, and engineer a system with over 1,300-fold activation. Finally, we apply DNA-binding domain swapping to screen uncharacterized Shewanella oneidensis TCSs in Escherichia coli, leading to the discovery of a previously uncharacterized pH sensor. This work should accelerate fundamental TCS studies and enable the engineering of a large family of genetically encoded sensors with diverse applications.
View details for DOI 10.1038/s41589-019-0286-6
View details for Web of Science ID 000472625600013
View details for PubMedID 31110305