Biochemistry and Molecular Biology
Penn State Science
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Thomas K. Wood

Thomas K. Wood

Main Content

  • Endowed Biotechnology Chair
  • Professor of Chemical Engineering and
  • Professor of Biochemistry and Molecular Biology
Office: 161 Fenske Laboratory
Lab: 303 Althouse Laboratory
University Park, PA 16802
Phone: (814) 863-4811

Research Interests

  • Discovering the genetic basis of biofilm formation with E. coli and P. aeruginosa
  • Discerning the role of toxin/antitoxin systems and cryptic prophages
  • Evolving biofilm regulators to control biofilm formation for biorefineries
  • Evolving bidirectional hudrogenases for hydrogen production
  • Understanding interkingdom cell communication

Graduate Programs

BMMB, CHEM E

Research Summary

Physiological relevance of Toxin/Antitoxin Systems

Nearly all sequenced bacterial genomes contain toxin/antitoxin (TA) systems (many have redundant systems such as E. coli which has 37 TA systems) but their physiological role has been debated.  Our group has discovered that both toxins and antitoxins are regulators that control vital elements of cell physiology including the stress response, tolerance to antibiotics (i.e., formation of persister cells), and biofilm formation. We focus on the mRNA endonuclease MqsR (toxin) and its protein antitoxin MqsA to discern how these systems help regulate cell function.  We have found that MqsR is a global regulator by controlling which mRNAs are degraded during stress (differential mRNA decay), and MqsA is a global regulator through its control of the stationary-phase sigma factor RpoS.  We continue to strive to understand the physiological relevance of these ubiquitous systems by characterizing novel TA systems as well as by understanding the role of TA systems in antibiotic resistance and biofilm formation.

Genetic
basis of biofilm formation 

Genetic basis of biofilm formation

Bacteria alternate between planktonic (free-swimming) and sessile states, with dense, multi-cellular communities called ‘biofilms’ being the more important state.  Nearly all cells make biofilms, which are formed in aquatic environments by the attachment of bacteria to submerged surfaces, to the air/liquid interface, and to each other. Biofilms attach via appendages, such as fimbriae and flagella, and microcolonies are formed by the production of microbial products including polysaccharides, proteins, lipids, and DNA.  Hundreds of genes are differentially controlled during biofilm development including stress-associated genes; hence, these systems present an interesting challenge in terms of their control. Although complex and not fully understood (for example, many bacteria possess redundant means to form biofilms), biofilm formation is an ordered process dependent on the response of the cell to environmental cues which in turn regulates specific genes.  Stages of biofilm formation include motility to the surface, attachment, formation of clusters, development of differentiated structures, and dispersal. Our group combines systems biology approaches (e.g., transcriptomics, proteomics) with protein structure determinations (through our collaborators  Wolfgang Peti and Rebecca Page at Brown University) to determine the genetic basis of biofilm formation.

 

Controlling biofilm formation for engineering applications

Anywhere water is in the liquid state, bacteria will exist as biofilms, which are complex communities of cells cemented together.  Although frequently associated with disease and biofouling, biofilms are also important for engineering applications, such as remediation, biocorrosion, biocatalysis and microbial fuel cells.  The robust nature of biofilms (i.e. their ability to withstand chemical and physical stresses more than their planktonic counterparts) makes them superior for many beneficial biotechnology applications.  Based on a better understanding of the genetic basis of biofilm formation, we find that biofilms may be controlled by manipulating extracellular signals and that they may be dispersed using conserved intracellular signals and regulators.  If we can control biofilms, then they may be formed at specific locations where they may be engineered to fight disease and to make chemicals in biorefineries.  As a demonstration of the ability to control biofilm formation, our group engineered the global regulator Hha and cyclic diguanylate-binding BdcA (a protein we discovered and characterized) to create proteins that enable biofilm dispersal. We then devised a biofilm circuit that utilizes these two dispersal proteins along with a population-driven quorum sensing switch. With this synthetic circuit, in a novel microfluidic channel, we formed an initial colonizer biofilm, introduced a second cell type (dispersers) into this existing biofilm, formed a robust dual-species biofilm, and displaced the initial colonizer cells in the biofilm with an extra-cellular signal from the disperser cells. We also removed the disperser biofilm with a chemically-induced switch, and the consortial population could be tuned. Therefore, cells have been engineered that are able to displace an existing biofilm and then these cells may be removed on command allowing one to control consortial biofilm formation for various applications.  Currently we are developing biofilm consortia for green chemistry.

biofilm consortia for green chemistry. 

Selected Publications

  • “Synthetic quorum-sensing circuit t control consortial biofilm formation and dispersal in a microfluidic device,” S. H. Hong, M. Hegde, J. Kim, X. Wang, and T. K. Wood, Nature Communications 3:613, 2012.
  • "Bacterial persistence increases as environmental fitness decreases," S. H. Hong, X. Wang, H. F. O'Connor, M. J. Benedik and Thomas K. Wood, Microbial Biotechnology on-line, 2012.
  • “Antitoxin MqsA Helps Mediate the Bacterial General Stress Response,” X. Wang, Y. Kim, S. H. Hong, Q. Ma, B. L. Brown, M. Pu, A. M. Tarone, M. J. Benedik, W. Peti, R. Page, and T. K. Wood, Nature Chemical Biology 7:359, 2011.
  • "Engineering biofilm formation and dispersal," T. K. Wood, S. H. Hong, and Q. Ma, Trends in Biotechnology 29: 87-94, 2011.
  • "Quorum quenching quandary: resistance to antivirulence compounds," T. Maeda, R. Garcia-Contreras, M. Pu, L. Sheng, L. R. Garcia, M. Tomas, and T. K. Wood, Nature ISME Journal. Online, 2011.
  • "Antitoxin DinJ influences the general stress response through transcript stabilizer CspE," Y. Hu, M. J. Benedik and T. K. Wood, Environmental Microbiology on-line, 2011.
  • "Toxin/Antitoxin Systems Influence Biofilm and Persister Cell Formation and the General Stress Response," X. Wang and T. K. Wood, Applied and Environmental Microbiology 77: 5577-5583, 2011.
  • “Cryptic Prophages Help Bacteria Cope with Adverse Environments,” X. Wang, Y.  Kim, K. Pokusaeva, J. M. Sturino, and T. K. Wood, Nature Communications 1:147, 2010.