Academic Appointments

  • Present 2006

    Founding Chair

    University of Maryland, Fischell Department of Bioengineering

  • 2006 2002

    Director, Bioengineering Graduate Program

    University of Maryland, Glenn L. Martin Institute of Technology

  • 2006 1994

    Director, Bioprocess Scaleup Facility

    University of Maryland, Glenn L. Martin Institute of Technology

  • 1994 1989

    Asst., Assoc., Full Professor

    University of Maryland, Department of Chemical and Biomolecular Engineering

Education

  • Ph.D. 1989

    Ph.D. in Chemical Engineering

    University of Colorado, Boulder

  • M.Eng.1983

    Master of Engineering in Chemical Engineering

    Cornell University

  • B.S.1982

    Bachelor of Science in Chemical Engineering

    Cornell University

Honors and Awards

  • 2014
    Marvin Johnson Award, American Chemical Society (ACS)
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    The Marvin J. Johnson Award in Microbial and Biochemical Technology, to recognize outstanding research contributions to microbial and biochemical technology.
    The Award is presented by the Division of Biochemical Technology at the Spring meeting of the American Chemical Society. The Award was established in 1978 and is currently sponsored by Pfizer.
  • 2013
    Charles Thom Award, Society of Industrial Microbiology and Biotechnology (SIMB)
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    This award is given to recognize individuals who have made one or more outstanding research contributions in industrial microbiology and/or biotechnology. These contributions should be of exceptional merit, reflecting an independence of thought and originality that adds appreciably to scientific knowledge. Activities such as journal editing, organizing and chairing conferences, and serving scientific societies in official capacities also may be considered when judging research contributions. However, the most important factor in selecting nominees for this Award is research accomplishments.
  • 2013
    Elected Fellow, American Chemical Society (ACS)
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    The American Chemical Society (ACS) Fellows Program was created by the ACS Board of Directors in December 2008 to recognize members of ACS for outstanding achievements in and contributions to science, the profession, and the Society.
  • 2012
    The American Institute of Chemical Engineers (AIChE) Food, Pharmaceutical and Bioengineering Division (FP&BE) Award in Chemical Engineering
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    Recognizes an individual's outstanding chemical engineering contribution in the food, pharmaceutical and/or bioengineering field, of fundamental nature and/or of practical significance to industry and industrial practice. These contributions may have been made in industry, government, or academic settings, or with other organizations.
  • 2011
    Elected Vice President At-Large, American Institute for Medical and Biological Engineering, 2011-2013
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    The American Institute for Medical and Biological Engineering (AIMBE) is a non-profit organization headquartered in Washington, D.C., representing 50,000 individuals and the top 2% of medical and biological engineers. In addition, AIMBE represents academic institutions, private industry, and professional engineering societies. AIMBE was founded in 1991 and its current vision is to provide leadership and advocacy in medical and biological engineering for the benefit of society.
  • 2007
    Elected Fellow, American Academy of Microbiology
    Over the last 50 years, 2,700 distinguished scientists have been elected to the Academy. Fellows are elected through a highly selective, annual, peer review process, based on their records of scientific achievement and original contributions that have advanced microbiology. A Committee on Elections, consisting of Fellows of the Academy who are elected by the membership, reviews all nominations for Fellowship and recommends to the Board of Governors what action should be taken.
  • 2001
    Elected Fellow, American Association for the Advancement of Science
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    A member whose efforts on behalf of the advancement of science or its applications are scientifically or socially distinguished and who has been a continuous member for the four year period leading up to the year of nomination, may, by virtue of such meritorious contribution be elected a Fellow by the Council. Examples of areas in which nominees may have made significant contributions are research; teaching; technology; services to professional societies; administration in academe, industry, and government; and communicating and interpreting science to the public. Fellows are elected annually by the AAAS Council from the list of approved nominations from the Section Steering Committees.
  • 2001
    Elected Fellow, American Institute for Medical and Biological Engineering
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    AIMBE’s College of Fellows includes around 1,500 individuals who have made significant contributions to the medical and biological engineering (MBE) community whether in academia, industry, or government and their contributions to MBE research, industry practice, and education have transformed the world.

The Research Group

2014

Back row: David Quan, Haig Pakhchanian, Amin Zargar, Naren Bhokisham, Tanya Gordonov, Niketa Jani, Milad Emamian, Jessica Terrell, William Bentley, Chen-Yu Tsao
Front row: Hsuan-Chen Wu, Nathan Barber, Hana Ueda, Melissa Rhoads, Chelsea Virgile, Steve Graff
Not pictured: 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
Not pictured: 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
Not pictured: Major Chris Byrd, Darryl Sampey, Xiaolong Luo

Ph.D. Alumni

  Yung Fei Ko, Ph.D., 1992, President Chang Gung Biotechnology Corp., Inc., Taiwan (co-advsior)
  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., J.D., 1999, 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

Research Associates and Visiting Professors

  David A. Lindsay, 1995, MedImmune, Inc., MD
  Min-Ying Wang, 1995, Professor, Chung-Hsing University, Taiwan
  Michael Ciocci, 1995-1996, The Chemistry Research Solution, LLC,. Widener University, PA
  Takeshi Gotoh, 1996-1997, Professor, Akita University, Japan
  Hyung Joon Cha, 1997-1999, Professor, POSTECH University, Pohang, South Korea
  Hae Jeong Chae, 1998-2000, Professor, Hoseo University, South Korea
  Guneet Kumar, 1998 – 2002, LifeTime Pharmaceuticals, Inc., MD
  Chi-Fang Wu, 2000- 2002, Beckton Dickinson, San Diego, CA
  Yoshifumi Hashimoto, 2003 – 2003, Protein Sciences Corp., CT
  Hyunmin Yi, 2003-2005, Assoc. Prof., Tufts University, MA
  Eunjeong (Katie) Kim, 2004-2006, Assoc. Prof., KRIST, S. Korea
  Hosan Kim, 2006-2006, DOD, Arlington VA
  Matthew Wook Chang, 2003-2007, Associate Professor, National University of Singapore, Singapore
  Sara Hooshangi, 2007-2009, Director, George Washington U
  Hyeung-jin Jang, 2006-2009, Assoc. Professor, Kyung Hee University, S. Korea
  Chantal Nde, 2007-2010, Kraft Foods, Inc., IL
  Bryn Adams, 2008-2011, Army Research Laboratory, Adelphi, MD
  Chen-Yu Tsao, 2008 – present, University of Maryland, MD
  Xiaolong Luo, 2011-2013, Asst. Prof. Catholic University, Washington DC
  Karen Carter, 2011 – 2014, IL
  Hsuan-Chen Wu, 2012 – 2015, Asst. Prof. National Taiwan University, Taipei, TW
  Niketa Jani, 2012 – 2014, State of Maryland Health Services, Baltimore, MD
  Simran Kaur, 2014-2015, U.S. Food and Drug Administration, MD
  Pricilla Hauk, 2014 - present

Research Projects

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    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?"

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    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).

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    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. For a glimpse of some of these activities, please visit the Biochip Collaborative web site.

Sort by year:

Directed Assembly of a Bacterial Quorum (2015)

Matthew D Servinsky, Jessica L Terrell, Chen-Yu Tsao, Hsuan-Chen Wu, David N Quan, Amin Zargar, Patrick C Allen, Christopher M Byrd, Christian J Sund, William E Bentley
Journal Paper The ISME Journal

Abstract

Many reports have elucidated the mechanisms and consequences of bacterial quorum sensing (QS), a molecular communication system by which bacterial cells enumerate their cell density and organize collective behavior. In few cases, however, the numbers of bacteria exhibiting this collective behavior have been reported, either as a number concentration or a fraction of the whole. Not all cells in the population, for example, take on the collective phenotype. Thus, the specific attribution of the postulated benefit can remain obscure. This is partly due to our inability to independently assemble a defined quorum, for natural and most artificial systems the quorum itself is a consequence of the biological context (niche and signaling mechanisms). Here, we describe the intentional assembly of quantized quorums. These are made possible by independently engineering the autoinducer signal transduction cascade of Escherichia coli (E. coli) and the sensitivity of detector cells so that upon encountering a particular autoinducer level, a discretized sub-population of cells emerges with the desired phenotype. In our case, the emergent cells all express an equivalent amount of marker protein, DsRed, as an indicator of a specific QS-mediated activity. The process is robust, as detector cells are engineered to target both large and small quorums. The process takes about 6 h, irrespective of quorum level. We demonstrate sensitive detection of autoinducer-2 (AI-2) as an application stemming from quantized quorums. We then demonstrate sub-population partitioning in that AI-2-secreting cells can ‘call’ groups neighboring cells that ‘travel’ and establish a QS-mediated phenotype upon reaching the new locale.

Geminal Dihalogen Isosteric Replacement in Hydrated AI-2 Affords Potent Quorum Sensing Modulators (2015)

Min Guo, Yue Zheng, Jessica L Terell, Michal Ad, Clement Opoku-Temeng, William E Bentley, Herman O Sintim
Journal Paper Chemical Communications, Volume 51, Pages 2617-2620

Abstract

Hydrated carbonyl groups in AI-2, a quorum sensing autoinducer, make key hydrogen bonding interactions in the binding site of LsrR (a transcriptional regulator). This can be recapitulated with geminal dibromides, via halogen bonding. Geminal dihalogens represent interesting isosteric replacements for hydrated carbonyls in ligands and are currently under-utilized in ligand design.

Electronic Modulation of Biochemical Signal Generation (2014)

Tanya Gordonov, Eunkyoung Kim, Yi Cheng, Hadar Ben-Yoav, Reza Ghodssi, Gary Rubloff, Jun-Jie Yin, Gregory F Payne, William E Bentley
Journal Paper Nature Nanotechnology, Volume 9, Pages 605-610

Abstract

Microelectronic devices that contain biological components are typically used to interrogate biology rather than control biological function. Patterned assemblies of proteins and cells have, however, been used for in vitro metabolic engineering, where coordinated biochemical pathways allow cell metabolism to be characterized and potentially controlled on a chip. Such devices form part of technologies that attempt to recreate animal and human physiological functions on a chip and could be used to revolutionize drug development. These ambitious goals will, however, require new biofabrication methodologies that help connect microelectronics and biological systems and yield new approaches to device assembly and communication. Here, we report the electrically mediated assembly, interrogation and control of a multi-domain fusion protein that produces a bacterial signalling molecule. The biological system can be electrically tuned using a natural redox molecule, and its biochemical response is shown to provide the signalling cues to drive bacterial population behaviour. We show that the biochemical output of the system correlates with the electrical input charge, which suggests that electrical inputs could be used to control complex on-chip biological processes.

Integrating Artificial with Natural Cells to Translate Chemical Messages that Direct E. coli Behavior (2014)

Roberta Lentini, Silvia Perez Santero, Fabio Chizzolini, Dario Cecchi, Jason Fontana, Marta Marchioretto, Cristina Del Bianco, Jessica L Terrell, Amy C Spencer, Laura Martini, Michele Forlin, Michael Assfalg, Mauro Dalla Serra, William E Bentley, Sheref S Mansy
Journal Paper Nature Communications, Volume 5

Abstract

Previous efforts to control cellular behaviour have largely relied upon various forms of genetic engineering. Once the genetic content of a living cell is modified, the behaviour of that cell typically changes as well. However, other methods of cellular control are possible. All cells sense and respond to their environment. Therefore, artificial, non-living cellular mimics could be engineered to activate or repress already existing natural sensory pathways of living cells through chemical communication. Here we describe the construction of such a system. The artificial cells expand the senses of Escherichia coli by translating a chemical message that E. coli cannot sense on its own to a molecule that activates a natural cellular response. This methodology could open new opportunities in engineering cellular behaviour without exploiting genetically modified organisms.

Redox-Capacitor to Connect Electrochemistry to Redox-Biology (2014)

Eunkyoung Kim, W Taylor Leverage, Yi Liu, Ian M White, William E Bentley, Gregory F Payne
Journal Paper Analyst, Volume 139, Pages 32-43

Abstract

It is well-established that redox-reactions are integral to biology for energy harvesting (oxidative phosphorylation), immune defense (oxidative burst) and drug metabolism (phase I reactions), yet there is emerging evidence that redox may play broader roles in biology (e.g., redox signaling). A critical challenge is the need for tools that can probe biologically-relevant redox interactions simply, rapidly and without the need for a comprehensive suite of analytical methods. We propose that electrochemistry may provide such a tool. In this tutorial review, we describe recent studies with a redox-capacitor film that can serve as a bio-electrode interface that can accept, store and donate electrons from mediators commonly used in electrochemistry and also in biology. Specifically, we (i) describe the fabrication of this redox-capacitor from catechols and the polysaccharide chitosan, (ii) discuss the mechanistic basis for electron exchange, (iii) illustrate the properties of this redox-capacitor and its capabilities for promoting redox-communication between biology and electrodes, and (iv) suggest the potential for enlisting signal processing strategies to “extract” redox information. We believe these initial studies indicate broad possibilities for enlisting electrochemistry and signal processing to acquire “systems level” redox information from biology.

Crystal Structures of the LsrR Proteins Complexed with Phospho-AI-2 and Two Signal-Interrupting Analogs Reveal Distinct Mechanisms for Ligand Recognition (2013)

Jung-Hye Ha, Yumi Eo, Alexander Grishaev, Min Guo, Jacqueline AI Smith, Herman O Sintim, Eun-Hee Kim, Hae-Kap Cheong, William E Bentley, Kyoung-Seok Ryu
Journal Paper Journal of the American Chemical Society, Volume 135, Pages 15526-15535

Abstract

Quorum sensing (QS) is a cell-to-cell communication system responsible for a variety of bacterial phenotypes including virulence and biofilm formation. QS is mediated by small molecules, autoinducers (AIs), including AI-2 that is secreted by both Gram-positive and -negative microbes. LsrR is a key transcriptional regulator that governs the varied downstream processes by perceiving AI-2 signal, but its activation via autoinducer-binding remains poorly understood. Here, we provide detailed regulatory mechanism of LsrR from the crystal structures in complexes with the native signal (phospho-AI-2, D5P) and two quorum quenching antagonists (ribose-5-phosphate, R5P; phospho-isobutyl-AI-2, D8P). Interestingly, the bound D5P and D8P molecules are not the diketone forms but rather hydrated, and the hydrated moiety forms important H-bonds with the carboxylate of D243. The D5P-binding flipped out F124 of the binding pocket, and resulted in the disruption of the dimeric interface-1 by unfolding the α7 segment. However, the same movement of F124 by the D8P′-binding did not cause the unfolding of the α7 segment. Although the LsrR-binding affinity of R5P (Kd, ∼1 mM) is much lower than that of D5P and D8P (∼2.0 and ∼0.5 μM), the α-anomeric R5P molecule fits into the binding pocket without any structural perturbation, and thus stabilizes the LsrR tetramer. The binding of D5P, not D8P and R5P, disrupted the tetrameric structure and thus is able to activate LsrR. The detailed structural and mechanistic insights from this study could be useful for facilitating design of new antivirulence and antibiofilm agents based on LsrR.

Nature's Other Self-Assemblers (2013)

William E Bentley, Gregory F Payne
Journal Paper Science, Volume 341, Pages 136-137

Abstract

There is a continuing quest to precisely fabricate soft matter for emerging opportunities in the medical and life sciences. Often this quest looks to nature as a source of materials or inspiration, and often the journey leads to polypeptides, nucleic acids, or their mimics. On page 154 of this issue, Ejima et al. (1) look elsewhere to find another self-assembling biological material—a search based on phenolics.

Autonomous bacterial localization and gene expression based on nearby cell receptor density (2013)

Hsuan‐Chen Wu, Chen‐Yu Tsao, David N Quan, Yi Cheng, Matthew D Servinsky, Karen K Carter, Kathleen J Jee, Jessica L Terrell, Amin Zargar, Gary W Rubloff, Gregory F Payne, James J Valdes, William E Bentley
Journal Paper Molecular Systems Biology, Volume 9, Page 636

Abstract

Escherichia coli were genetically modified to enable programmed motility, sensing, and actuation based on the density of features on nearby surfaces. Then, based on calculated feature density, these cells expressed marker proteins to indicate phenotypic response. Specifically, site‐specific synthesis of bacterial quorum sensing autoinducer‐2 (AI‐2) is used to initiate and recruit motile cells. In our model system, we rewired E. coli's AI‐2 signaling pathway to direct bacteria to a squamous cancer cell line of head and neck (SCCHN), where they initiate synthesis of a reporter (drug surrogate) based on a threshold density of epidermal growth factor receptor (EGFR). This represents a new type of controller for targeted drug delivery as actuation (synthesis and delivery) depends on a receptor density marking the diseased cell. The ability to survey local surfaces and initiate gene expression based on feature density represents a new area‐based switch in synthetic biology that will find use beyond the proposed cancer model here.

Biological nanofactories target and activate epithelial cell surfaces for modulating bacterial quorum sensing and interspecies signaling (2010)

Colin G Hebert, Apoorv Gupta, Rohan Fernandes, Chen-Yu Tsao, James J Valdes, William E Bentley
Journal Paper ACS Nano, Volume 4, Pages 6923-6931

Abstract

In order to control the behavior of bacteria present at the surface of human epithelial cells, we have created a biological “nanofactory” construct that “coats” the epithelial cells and “activates” the surface to produce the bacterial quorum sensing signaling molecule, autoinducer-2 (AI-2). Specifically, we demonstrate directed modulation of signaling among Escherichia coli cells grown over the surface of human epithelial (Caco-2) cells through site-directed attachment of biological nanofactories. These “factories” comprise a fusion protein expressed and purified from E. coli containing two AI-2 bacterial synthases (Pfs and LuxS), a protein G IgG binding domain, and affinity ligands for purification. The final factory is fabricated ex vivo by incubating with an anti-CD26 antibody that binds the fusion protein and specifically targets the CD26 dipeptidyl peptidase found on the outer surface of Caco-2 cells. This is the first report of the intentional “in vitro” synthesis of bacterial autoinducers at the surface of epithelial cells for the redirection of quorum sensing behaviors of bacteria. We envision tools such as this will be useful for interrogating, interpreting, and disrupting signaling events associated with the microbiome localized in human intestine and other environments.

Engineered biological nanofactories trigger quorum sensing response in targeted bacteria (2010)

Rohan Fernandes, Varnika Roy, Hsuan-Chen Wu, William E Bentley
Journal Paper Nature Nanotechnology, Volume 5, Pages 213-217

Abstract

Biological nanofactories, which are engineered to contain modules that can target, sense and synthesize molecules, can trigger communication between different bacterial populations. These communications influence biofilm formation1, 2, virulence3, 4, bioluminescence5, 6 and many other bacterial functions7, 8 in a process called quorum sensing9. Here, we show the assembly of a nanofactory that can trigger a bacterial quorum sensing response in the absence of native quorum molecules. The nanofactory comprises an antibody (for targeting) and a fusion protein that produces quorum molecules when bound to the targeted bacterium. Our nanofactory selectively targets the appropriate bacteria and triggers a quorum sensing response when added to two populations of bacteria. The nanofactories also trigger communication between two bacterial populations that are otherwise non-communicating. We envision the use of these nanofactories in generating new antimicrobial treatments that target the communication networks of bacteria rather than their viability.

Current Courses

  • Present 2014

    BIOE 120 Biology for Engineers

    A combination of lectures and discussions covering biology from a utilization perspective, and lectures on illustrative mathematical models that capture the essences of characteristics of living entities. The biology material will focus on: distinguishing engineering from biological science, principles form the sciences applicable to biology, typical biological responses to environmental stimuli, scaling of biological responses, and different means to utilize living entities.

  • Present 2014

    BIOE 601 Biomolecular and Cellular Rate Processes

    Presentation of techniques for characterizing and manipulating non-linear biochemical reaction networks. Advanced topics to include mathematical modeling of the dynamics of biological systems; separation techniques for heat sensitive biologically active materials; and rate processes in cellular and biomolecular systems. Methods are applied to current biotechnological systems, some include: recombinant bacteria; plant, insect and mammalian cells; and transformed cell lines.

Office Hours

Dr. Bentley does not have posted office hours for the fall semester. Please send him an email or otherwise contact Ms. Karen Lasher.

Bioengineering Main Office

Dr. Bentley's office is located in the Fischell Department of Bioengineering main offices.

2226 Jeong H. Kim Engineering Building
University of Maryland, College Park, MD 20742

Labs

Dr. Bentley has two labs on campus, located in the plant sciences building. Rm. 6142

Plant Sciences Building
University of Maryland, College Park, MD 20742