William E. Bentley

2022

From Left to Right: William Bentley, Chen-Yu Chen, Eric VanArsdale, Sally Wang, Chen-Yu Tsao, Jinyang Li, Dana Motabar, Kayla Chun, Monica Chu, Futon Al-Jirafi, Rahma Zakaria (not pictured, Nick Pirolli)

2020

From Left to Right: Chen-Yu Chen, Eric VanArsdale, Dana Motabar, William Bentley, Sally Wang, So Hyun Ahn, Kayla Chun, Monica Chu, Rahma Zakaria (not pictured, Kristina Stephens, Chen-Yu Tsao, Ashley Chapin, Julie Pitzer)

2019

From Left to Right: Kristina Stephens, So Hyun Ahn, Dana Motabar, Kayla Chun, Ashley Chapin, Jinyang Li, Chen-Yu Tsao, Eric VanArsdale, Sally Wang, Rahma Zakaria, Chen-Yu Chen, Julie Pitzer

2016

From Left to Right: Tanya (Gordonov) Tschirhart, Wu Shang, Ryan McKay, William Bentley, Amin Zargar, Naren Bhokisham, David Quan, Melissa Rhoads, Jess Terrell, Kristina Stephens, Hana Ueda, Chelsea Virgile, Michelle Brookstaver

2014

From Left to Right: David Quan, Haig Pakhchanian, Amin Zargar, Naren Bhokisham, Tanya Gordonov, Niketa Jani, Milad Emamian, Jessica Terrell, William Bentley, Chen-Yu Tsao, Hsuan-Chen Wu, Nathan Barber, Hana Ueda, Melissa Rhoads, Chelsea Virgile, Steve Graff, John Kerwin, Kevin Knapstein, Darryll Sampey

2012

From Left to Right: Chen-Yu Tsao, David Quan, William Bentley, Tanya Gordonov, Karen Carter, Apoorv Gupta, Rodica Bauer, Jessica Terrell, Hsuan-Chen Wu, Xiaolong Luo, Amin Zargar, Darryl Sampey, John Kerwin

2010

From Left to Right: David Quan, Colin Hebert, Hsuan-Chen Wu, William Bentley, Karen Carter, Kai Wang, Sara Hooshangi, Chen-Yu Tsao, Rodica Bauer, Zhiqiang (Michael) Xiong, Varnika Roy, Bryn Adams, Major Chris Byrd, Darryl Sampey, Xiaolong Luo

  Yung Fei Ko, Ph.D., 1992, President Chang Gung Biotechnology Corp., Inc.
  Sarah W. Harcum, Ph.D., 1993, Professor, Dept. Bioengineering, Clemson University, SC
  Min-Ying Wang, Ph.D., 1994, Professor, Dept. Chemical Engineering, Chung Hsing University, Taiwan
  Delia M. Ramirez Leon, Ph.D., 1995, U.S. Patent Office, VA
  Tracey R. Pulliam-Holoman, Ph.D., , formerly Asst. Professor, Dept. Chemical Engineering, University of Maryland, MD
  Tsu-shun Lee, Ph.D., 1997, Sanofi Pasteur, Swiftwater, PA
  Yu-Chen Hu, Ph.D., 1999, Professor and Chair, Department of Chemical Engineering, National Tsing-Hua University, Taiwan
  Minh-Qhan Khuc Pham, Ph.D., 1999, J.D., Berenato & White, LLC
  Ryan T. Gill, Ph.D., 1999, Professor, Dept. of Chem. and Biol. Eng., University of Colorado, CO
  Chi-Fang Wu, Ph.D., 1999, Becton Dickinson, San Diego, CA
  Ranjan Srivastava, Ph.D., 1999, Associate Professor, Dept. of Chemical, Materials, and Biomolecular Engineering, University of Connecticut, CT
  Shu-Hua Chan, Ph.D., 2000, Northern VA (co-advisor)
  Matthew P. DeLisa, Ph.D., 2000, Professor, School of Chemical Engineering, Cornell University, NY
  Nimish G. Dalal, Ph.D., 2001, Bristol Myers Squibb, Syracuse, NY
  Shannon F. Kramer, Ph.D., 2002, Baylor University College of Dentistry, TX
  Hyunmin Yi, Ph.D., 2003, Assoc. Professor, Dept. of Chemical and Biological Engineering, Tufts University, MA
  Nicole A. Bleckwenn, Ph.D., 2004, MedImmune, Inc., Gaithersburg, MD
  Liang Wang, Ph.D., 2004, Superarray Biosciences, Rockville, MD
  John C. March, Ph.D., 2005, Assoc. Professor, Dept. Biological and Environmental Engineering, Cornell University, NY
  Songhee Kim, Ph.D., 2005, KIST, Seoul, S. Korea
  Chong Yung, Ph.D., 2005, Agilent, Inc., San Jose, CA
  Jun Li, Ph.D., 2006, USPTO, VA
  David Small, Ph.D., 2007, DCS Consulting, MD
  Angela T. Lewandowski, Ph.D., 2007, Bristol Myers Squibb, Boston, MA
  Chen-Yu Tsao, Ph.D., 2007, University of Maryland, College Park, MD
  Chi-Wei Hung, Ph.D., 2008, University of Maryland, Baltimore, MD
  Rohan Fernandes, Ph.D., 2008, Asst. Professor, Children’s National Medical Center, Washington, DC
  Colin G. Hebert, Ph.D., 2008, LumaCyte, Charlottesville, VA
  Karen Carter, Ph.D., 2011, Chicago, IL
  Christopher M. Byrd, Ph.D., 2011, Asst. Prof. U.S. Military Academy, West Point, NY
  Varnika Roy, Ph.D., 2011, MedImmune, Inc., MD
  Hsuan-Chen Wu, Ph.D., 2012, Asst. Prof., Dept. Biochemical Science & Technology, National Taiwan University, Taiwan
  David Nathan Quan, Ph.D., 2015, University of Maryland, College Park, MD
  Amin Zargar, Ph.D., 2015, University of Maryland, College Park, MD
  Jessica Terrel, Ph.D., 2015, Army Research Laboratory, Adelphi, MD
  Tanya (Gordonov) Tschirhart, Ph.D., 2015, Navy Research Laboratory, Washington, DC
  Hana Ueda, Ph.D., 2016, Los Angeles, CA
  Melissa Rhoads, Ph.D., 2016, Lockheed Martin, VA
  Darryl Sampey, Ph.D., 2016, BioFactura, Frederick, MD
  John Kerwin, Ph.D., 2017, IBBR/NIST, Shady Grove, MD

• 

  Metabolic and Biomolecular Engineering

  Quorum Sensing and cell networks

  We create molecular tools to understand the regulation of genetic curcuits during applied stresses. We also use transcriptional promoter probes, quantitative RT-PCR, Western analyses to gain near real time information on the dynamics of metabolites, genes, proteins, and protein assemblies in targeted circuits.

  One objective is to alter the intracellular environment to improve cellular processes, including the production of recombinant proteins. In order to make use of the vast quantities of data, we need to organize them in reduced dimensional space, develop appropriate mathematical models, and then ultimately control phenotypic behavior. This is a component of Systems Biology. We are also actively pursuing transient metabolic controllers to minimize pleiotropy. This is a component of Synthetic Biology. We incorporate signal transduction modalities and RNA controllers to modulate, in vivo, the level of specific regulatory proteins, and downstream proteins in cascaded control loops. We are also the first group to develop a means to control bacterial subpopulations and sort quantized quorums based on QS signaling (see Servinsky et al., ISME Journal, 2015). With this technology we can answer questions like 'How many bacteria of our group should seek out new and better territories?' or 'If our entire population is challenged with an antibiotic, should we all make resistance proteins or just a few, so our colony survives in the long run?'

  

  One exciting target is a newly characterized signal transduction pathway that communicates cell population, enabling individual bacteria to act with multicellularity. This phenomenon, also known as 'quorum sensing, (QS)', results in cell-to-cell communication and plays a significant role in regulating cell behavior. In the LuxS-mediated signaling system of E. coli, we are the first group to explore the impact of AI-2 on the transcriptome (Delisa et al., J. Bact, 2001; Wang et al., J. Bact. 2005) and we are the first group to elucidate the impact of quorum regulator, LsrR and kinase, LsrK (Li, et. al., J. Bact. 2007). We are the first group to mathematically model quorum circuitry (Li, et. al., Nature Mol. Sys. Biol., 2006). Our efforts to develop innovative controllers of signal transduction have yielded biological nanofactories that bring biochemical enzyme activities to the outer surfaces of cells so that molecules can be synthesized directly where they can be used…in our case to interrupt bacterial communication (Fernandes et al., Nature Nanotech., 2010). Current efforts include deciphering LuxS regulated genes and the impact of QS on the intracellular biomolecular landscape that influences protein synthesis; we have created a completely new system for expressing proteins that requires no operator input or sampling (Tsao et al., Met. Eng., 2010).

  Finally, because we have exploited signaling pathways to control individual and groups of cells, we engineered bacteria to seek out and kill pathogens, namely, Pseudomonas aeruginosa, in the GI tract of mice. (Hwang et al., Nature Comm., 2017). This notion of synthetic biology is different than small molecule generation – the more common objective of synthetic biology. In our view, the cells themselves can be the functioning products of synthetic biology in that they can recognize, compute, actuate, and deliver, all in a programmed manner.

• 

  Biofabrication Engineering of Biological Signaling

  (bBIOS)

  We are engaged in a multidisciplinary effort to create systems that serve to bridge the communication gap between biology and electronic microfabricated devices. Since biology “communicates” via small molecule signaling (like in quorum sensing above) and ion flow and because we can program devices with electrons, we have a problem in translation. We employ Nature’s second most abundant biopolymer, chitosan, to serve as a “smart” stimuli-responsive interface. We are generating a biofabrication "tool box" that enables the assembly of complex biological structures onto programmable devices that allows for the accurate interrogation of the biological system. In our case, quorum sensing and bacterial communication (and even cross-Kingdom signaling) serves as a wonderful test bed for listening in on biology. We are developing all sorts of new methods for localizing DNA, proteins, cells and cell assemblies onto devices that will serve to break down complexities so that discoveries can be attributed to specific molecules, gradients, patterns, etc. With Sheref Mansy's group in Italy, we have created "artificial cells" that were able to interpret non-native chemical cues and release biological effector molecules that altered naturally growing bacterial cells. (Lentini et al., Nature Comm., 2014). We anticipate developing new tools for deciphering the presence of pathogens, for understanding and treating metabolic diseases, cancer, and hemorrhagic shock.

  Finally, we have developed a means to electronically assemble and control the activity of a two-enzyme biosynthetic pathway that leads to the bacterial QS autoinducer, AI-2 (Gordonov et al., Nature Nanotech., 2014). This showed for the first time that one can electrically connect to and control biological behavior—as our signal molecule generated and controlled on chip determines behavioral phenotype at the population level. We have also for the first time, demonstrated direct electrical actuation of gene expression in bacteria. We exploited redox signaling, but actuated in a reversible manner expression of several genes in E. coli, including those that synthesize native signaling molecule, AI-1. This molecule, in turn, actuated gene expression in neighboring cells. Hence, electrically programmed cells were made to stimulate signaling via native biological means. (Tshirhart et al., Nature Comm., 2017). For a glimpse of some of these activities, please visit the <a href="http://biochip.umd.edu/">Biochip Collaborative web site</a>.