Their latest achievement, detailed in a paper published in the January 21 issue of the journal Nature, is a crucial step in creating genetic sensors that might one day provide humans with advance information about temperature, poisons and other potential hazards in the environment by monitoring changes in the bacterium’s blinking rates.

“Programming living cells is one defining goal of the new field of synthetic biology,” said Jeff Hasty, associate professor of biology and bioengineering at UCSD who headed the research team with Lev Tsimring, associate director of UCSD’s BioCircuits Institute.

“Dr. Hasty and colleagues have used powerful genetic tools, backed by decades of detailed knowledge of bacterial processes, to create a system that delivers on the promise of synthetic biology — to engineer living organisms to meet pressing societal needs,” said James Anderson, who oversees computational biology grants at the NIH’s National Institute of General Medical Sciences. “The oscillating system they engineered sets the stage for the development of highly sensitive sensors that could have multiple applications in basic research, biotechnology and medicine.”

“Synchronization of clocks and oscillators in general has been a fascinating subject for physicists and applied mathematicians for centuries,” said Tsimring. “This began with the Dutch mathematician and astronomer Christiaan Huygens, who is credited with its serendipitous discovery in 1665 when he suspended a pair of nearly identical pendulum clocks (which he invented and patented some 8 years earlier) on the same wooden beam.”

“Synchronization plays a crucial role in physics and biology as a way of self-organization of highly regular behavior with less that perfect components. This phenomenon has a myriad of applications in modern technology, from communication networks to GPS. Our study demonstrates how inherently noisy gene oscillators can operate together with beautiful synchronicity and regularity once coupled together in a specific way.”

Over the past decade, researchers have gone from wiring genetic toggle switches and oscillators in living cells to building living circuits capable of pattern generation, noise shaping, edge detection and event counting. In their latest development, the UCSD researchers took advantage of a type of bacterial communication in which bacteria exchange small molecules.

“Many bacteria species are known to communicate by a mechanism known as quorum sensing, that is, relaying between them small molecules to trigger various behaviors,” said Hasty. “Other bacteria are known to disrupt this communication mechanism by degrading these relay molecules.”

Taking these communication elements from different organisms, Hasty and his team of researchers — who included UCSD bioengineering graduate students Tal Danino and Octavio Mondragon — designed and constructed a network in the genetic model bacterium E. coli with positive and negative feedback components to produce a colony of synchronized clocks.

Hasty said the architecture of the circuit is similar to his team’s previous genetic clock (see: here), but with the quorum sensing components allowing the phase information — that is, the oscillations between the bacterial cells — to be relayed.

The researchers constructed devices to precisely control the sizes of the bacterial colonies between two different scales: a micron, or a millionth of a meter, and a millimeter, or one-thousandth of a meter. At the micron scales, Hasty said the cells in the colonies oscillate synchronously from 50 to 90 minutes, a period that can be tuned externally. But at the longer, or millimeter scales, he noted, the time for diffusion of the signal becomes more important, allowing the researchers to actually observe the propagation of the signal through the colony.

“The use of quorum sensing is a promising approach to increase the sensitivity and robustness of the dynamic response to external signals,” said Hasty. “In nature, synchronization typically helps stabilize a desired behavior arising from a network of intrinsically noisy and unreliable elements. We think the synchronized genetic clock sets the stage for the use of microbes as a macroscopic biosensor with oscillatory output, or applications of using a synchronized periodic signal in drug delivery.”

The scientists received funding for their development from the National Institute of General Medical Sciences, which is part of the National Institutes of Health.

Put together by smoking experts and smokers themselves, much of the new kit aims to combat stress and cravings, as well as giving tips on how to avoid the triggers that lead to sparking up a fag in the first place.

“We know that certain triggers and cravings can threaten a successful quit,” said Professor Robert West from the Health Behaviour Research Centre at University College London.

“People need to find their own personal combination of support and tools to help combat them.”

The kit contains two mp3 downloads that the government believes are scientifically proven to reduce cravings, as well as a stress-relieving toy which smokers can handle and even a toothbrush.

There is also an appeal to household budgets, with a health/wealth wheel to help smokers work out how much money they are saving by quitting, and a 28-day wall planner to help them focus.

If this is not enough, there will also be a tug at the heartstrings with a new advertising campaign concentrating on the effect smoking has on loved ones.

The children of smokers, rather than actors, are seen singing the famous tune “I’d Do Anything” from the musical Oliver – the message being that they would go to any lengths to help parents to stop smoking.

The Department of Health claims that 96% of children whose parents smoke want them to quit.

The kits also contain details of where people can access nicotine replacement therapy such as gum or patches and tailored support.

In 2008-09, 337,054 people successfully quit smoking using help from the NHS, and public health minister Gillian Merron said that around seven out of ten smokers want to give up at any one time.

“NHS stop smoking services are rated as the best in the world, and smokers who quit by using free NHS support are up to four times more likely to be successful,” she added.

I had always liked science but by age 10, I had already decided that I wanted to be a veterinarian. However, after seeing the film Ben Hur at age 11—during which two of the main characters who have leprosy are miraculously cured—I fantasized what it might be like to be able to discover cures for infectious diseases. As corny as it may sound, the movie convinced me that my true calling in life wasn’t veterinary medicine but microbiology. Nevertheless, I attended Cornell University as a pre-veterinary medicine undergraduate with a dual major in animal science and microbiology. During my senior year at Cornell, Dr. Brooks Naylor, my food microbiology professor at the time, invited me to do a senior research project in his laboratory. After several weeks in the laboratory I was hooked and knew that graduate school and not veterinary school was in my future.

I entered graduate school in 1974 and did my PhD work in Bob Deibel’s laboratory in the Department of Bacteriology at the University of Wisconsin-Madison studying the pathogenesis of Salmonella gastroenteritis. Because Bob was Chairman of the Department and a food microbiology consultant, he wasn’t around much. This forced me to become self reliant and an independent investigator very early in my scientific career. Interestingly, when I started graduate school, my goal was to earn a PhD degree and teach microbiology at a small liberal arts college. However, after three years at Wisconsin, I decided to eschew a career as a science educator in favor of becoming a tenure track faculty member at a prestigious research institution.

I received my PhD degree in 1981and chose to do a postdoctoral fellowship with Stephen Morse in the Department of Microbiology at Oregon Health Sciences University where I investigated the pathogenesis of Neisseria gonorrhoeae. After two years in Stephen’s lab, I realized that the field of molecular biology had finally taken off and I needed to develop molecular biological skills to compete for my coveted tenure track faculty position. In 1984, I joined Howard Shuman’s laboratory as a postdoctoral fellow in the Department of Microbiology at the College of Physicians and Surgeons at Columbia University in New York City where I studied the molecular pathogenesis of Legionella pneumophila, the causative agent of Legionnaires Disease.

In 1987, after spending three more years as a postdoctoral fellow, my newly acquired molecular biology training coupled with a respectable publication record helped me to land a tenure track faculty position in the Department of Microbiology at the University Of Miami School Of Medicine. I spent the next seven years feverishly doing laboratory research, teaching medical and graduate students, publishing papers and mainly writing grants to establish an independent research program on the role of lipopolysaccharide in the molecular pathogenesis of L. pneumophila. While I was a productive researcher, who regularly published and was recognized on several occasions for teaching excellence, I failed to consistently win grant support to run my laboratory. Consequently, in 1994, I was denied tenure and forced to leave academia—an emotionally devastating event that that ended a life-long dream of becoming a world class research scientist.

Luckily, at that time, the American biotechnology industry had finally hit its stride and I landed a job as a scientist at a New Jersey-based biotechnology company where I managed an antibacterial drug discovery program. My time in industry—which lasted only two years—provided me a firm understanding of the business side of science and perhaps, more importantly, convinced me that industrial research wasn’t for me. This, coupled with a yearning desire to teach again, prompted me to successfully apply for a job as Chairperson of Biology at a local community college. While a good idea at the time, I quickly realized that while I still loved to teach, administration wasn’t my strong suit and I left the community college job after a year.

Unfortunately, by 1998, I had effectively exhausted most traditional career options for scientists with PhD degrees and I desperately needed a job—mainly because I had a wife and three young children to support. Fortunately, while working at the community college, I successfully helped several professional recruiters place new hires into jobs at biotechnology and pharmaceutical companies. This prompted me to seriously consider professional recruiting as a career option and in early 1999 I landed a job as a recruiter at a local recruiting firm. As a new hire I had to attend recruiter school for six weeks. Surprisingly, this training would prove to play a pivotal role in subsequent decisions that helped to shape my career.

After three successful years as professional recruiter, an Australian biotechnology company recruited and hired me as a science and business consultant to help guide their antibacterial drug discovery program. The new job led to an almost four year stint as an independent management consultant advising private and publicly-traded biotechnology companies on business, scientific and financial matters. Also during this time, I decided to indulge my own entrepreneurial fantasies and in 2001 I founded BioInsights (www.bioinsights.com), Inc, a bioscience education and training company. In 2003, Abe Abuchowski and I founded Prolong Pharmaceuticals (www.prolongpharmaceuticals.com) a drug delivery company with two drugs in early stage clinical development. Unfortunately, the rigorous demands of running BioInsights and starting Prolong ultimately led to the demise of my consulting practice and by 2004 I was forced to consider another career move.

Luckily, in 2002, I had begun to write for several biotechnology industry trade publications. Although I wasn’t getting paid to write, it enabled me to hone and polish my writing skills. In late 2004, a medical communications expert who I knew suggested that I take a stab at medical writing. At the time, I didn’t know much about medical writing but I quickly learned that it pays well and medical writers are always in demand. I took her advice and landed my first medical writing job in 2005. Since then, I have worked at a variety of medical communications agencies and pharmaceutical companies preparing manuscripts, posters, slide presentations and other work. Currently, I am freelance science and medical writer, blogger (www.biojobblog.com) and social media enthusiast who, along with Dr. Vincent Racaniello, started an online social networking site for bioscientists called BioCrowd (www.biocrowd.com)

Unlike most scientists, my career path has taken many unexpected twists and turns. I never intended it to be as eclectic or convoluted as it has turned out to be. Nevertheless, I believe that my unusual career trajectory has transformed me into a better rounded scientist than I would have been if I had been able to pursue my intended academic career. In retrospect, I attribute my career successes to solid problem solving skills, an unrelenting desire to continue to learn and an unwavering ability to take risks. Finally, and perhaps most important, I learned that there is no right or wrong career path in the life sciences—only the one that you choose for yourself!

Until next time…

Good Luck and Good Job Hunting!!!!

RESEARCH TRIANGLE PARK, N.C. – Enthalpy has announced Susan M. Deupree, Ph. D., as its postdoctoral fellow under the Industrial Fellowship Program (IFP) sponsored by the North Carolina Biotechnology Center.

The program places doctoral recipients with companies where they learn the complexities of running a biotechnology business. Enthalpy is one of three companies selected in 2009 for the program.

Deupree obtained her doctorate in Biological Chemistry from the University of North Carolina at Chapel Hill in 2009, where her dissertation focused on bioanalytical methods for investigating bacterial adhesion and the antibacterial action of nitric oxide. She has worked as a scientist in pharmaceutical research and development, and has lectured on analytical microscopy techniques. While at UNC, Deupree developed a novel method for measuring the strength of bacterial adhesion using atomic force microscopy.

“We are excited to have Dr. Dupree join us,” said Mike Allen, director of Enthalpy’s Bioanalytical Division. “She’ll be mentored by Brian Nofsinger, Ph.D., our associate director, and will work on projects with him initially. Once she’s introduced to our procedures, she will manage her own studies, work with our business development and marketing people, and will hopefully present for us at upcoming conferences. She has diverse capabilities and real-world experience, so we expect she will be a good fit with Enthalpy.”

“The Biotech Center’s Industrial Fellowship Program ties in well with our desire to be a good corporate citizen,” Allen said. “This program also gives Dr. Deupree the opportunity to work with some top-notch scientists at Enthalpy, and could ultimately lead to her working with us permanently.”

Funding for the IFP is provided by the State of North Carolina, through state budget allocations. Biotechnology companies are chosen for the program based on rigorous selection criteria that include company growth since inception and reputation in the business community in addition to scientific and technical considerations. The Biotechnology Center engages outside reviewers to score each applicant company on the selection criteria, with only top-scoring firms winning entry to the program.

“At the Biotech Center we leverage the strong partnerships we have with organizations in North Carolina, for example the Council for Entrepreneurial Development and the Small Business Technology Development Center,” said Shobha Parthasarathi, Ph.D., technology development director for the Biotechnology Center. “Fellows are given access to university business classes, various conferences on regulatory matters, intellectual property, and other issues. At the end of their fellowship, we make available an internship program to allow them to try other aspects of running a biotechnology business beyond simply pure R&D. By the time the fellows come out of the two-year program, they’re well-rounded in the entire business of biotechnology.”

“Ultimately, our goal is to reach a steady-state condition where we award funding for ten postdocs per year,” Parthasarathi added. “This year our budget was cut, so we were limited to three companies. But to the best of our knowledge, nowhere else in the world is state money being used to fund postdoctoral work in industry.”

ABOUT ENTHALPY ANALYTICAL, INC.
Enthalpy Analytical, Inc. was founded in 1993 to provide analytical support for the environmental and pharmaceutical industries. Enthalpy remains true to its mission of providing accurate, high-quality analytical services in a timely manner and for a reasonable cost.

Enthalpy’s Bioanalytical Division offers GLP-compliant LC/MS/MS bioanalytical services for all phases of drug discovery and development. The division provides responsive, reliable service supported by Enthalpy’s exclusive 70% Solution. The company holds scheduled projects at 70% of capacity to guarantee sufficient resources for meeting deadlines and expediting critical studies.

ABOUT THE NC BIOTECHNOLOGY CENTER
The NC Biotechnology Center is a private, nonprofit corporation supported by the North Carolina General Assembly. Its mission is to provide long-term economic and societal benefits to North Carolina through statewide support of biotechnology research, business, education, and strategic policy. Ncbiotech