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Battling Biofilm Infections through Basic Research

“Biofilms” are composed of single celled organisms that stick together on a surface – this includes bacteria embedded within self-produced slime that thrive in host organisms such as humans. The individual cells use chemical signaling to act as organized cooperative communities. Scientists study biofilms in part to understand the evolutionary process that led from single cells to interacting communities of cells and then to true multicellular organisms.

Biofilms are also studied because serious bacterial biofilm infections, such as pneumonia in cystic fibrosis patients, chronic wounds, and implant- and catheter-associated infections, afflict millions of people and, depending on the type of bacteria involved, kill many victims every year.

“The important hallmarks of chronic biofilm-based infections are extreme resistance to antibiotics and many other conventional antimicrobial agents, and an extreme capacity for evading the host defenses,” notes Gürol Süel, a microbiologist at the University of California, San Diego.

Süel has teamed up with Kerwyn Casey Huang, a theoretical physicist at Stanford University, to study the genetic makeup of bacteria in biofilms.

Specifically, Süel and Huang hope to test the hypothesis that growth in such a community can relieve the need of some bacteria for proteins that would otherwise be essential for their survival if they were on their own. They also hope to determine if proximity to a typical independent cell will affect the growth of a cell lacking an essential protein, whether through physical contact or chemical signaling.

To perform this research they will use advanced CRISPR/Cas technology developed in 2013 for precise gene editing and regulation. CRISPR – “clustered regularly interspaced short palindromic repeats” -- refers to short DNA base sequences followed by even shorter segments of “spacer” DNA. “Cas” refers to specific proteins that guide RNA into a cell to cut genes at specifically desired spacer locations.

Süel and Huang’s research is being funded through the Scialog program jointly sponsored by Research Corporation for Science Advancement (RCSA) and the Gordon and Betty Moore Foundation. Scialog supports research, intensive dialog and community building to address scientific challenges of global significance. Within each multi-year initiative, Scialog Fellows collaborate in high-risk discovery research on untested ideas and communicate their progress and form new collaborations in annual conferences.

Süel and Huang are participants in a two-year Scialog program entitled Molecules Come to Life. The program focuses on such questions as, what are the fundamental principles that make a collection of molecules within a cell produce behaviors that we associate with life? How do molecules combine and dynamically interact to form functional units in cells, and how do cells themselves interact to form more complex lifeforms?

The researchers formed their collaboration at a Scialog conference held earlier this year at Biosphere2 north of Tucson, Arizona. There, 50 or so leading young scientists from divergent fields of biology, physics and chemistry engaged in intensive discussions designed to produce creative ideas for innovative research.

“Scialog aims to encourage collaborations between theorists and experimentalists,” said RCSA Program Director Richard Wiener. “And, we encourage approaches that are driven by theory and coarse-grained modeling, that are testable by experiments.”

The next Molecules Come to Life Scialog conference will be held in March 2016. 

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