Small molecules, big honor

03/05/2012

Cynthia Sharma runs a junior research group at the University of Würzburg’s Center for Infection Research. She is now one of six excellent young scientists to be admitted by the Bavarian Academy of Sciences and Humanities to its "Förderkolleg", a program set up specifically to promote young talent.

They boast a hugely important research topic; it is expected that they will have a significant influence on future scientific developments; and they are both innovative and creative: these are the prerequisites that research projects must fulfill if they are to receive funding from the Bavarian Academy of Sciences and Humanities.

Scientists who apply to be admitted into the Academy’s Förderkolleg should also satisfy the following conditions: they must be no older than 34, they must live in Bavaria, and they must be working on their scientific career at a university or a non-university research institution in Bavaria. To be in this position, they must have completed a broad-based scientific education followed by an exceptional doctorate. At least, this is what the Academy says in one of its information flyers.

Cynthia Sharma’s research

Cynthia Sharma meets all these criteria: she is 33 years old, her doctoral thesis focusing on small regulatory RNAs in bacteria received the highest grade of “summa cum laude”, and, since June 2010, she has been running her own research group at the University of Würzburg’s Center for Infection Research. There, too, she is examining this particular type of ribonucleic acids in bacteria, concentrating mainly on two bacterial pathogens:

Helicobacter pylori, a bacterium carried by around half the world’s population, and Campylobacter jejuni, a related bacterium that is currently the most common cause of bacterial diarrheal diseases. “Helicobacter has the ability to survive in an acidic environment. As a result, it can colonize the human stomach and cause stomach ulcers and cancer there,” explains Sharma.

Surprising discovery

Cynthia Sharma’s primary interest lies in the molecular biological processes that occur in these bacteria. Two years ago, she and her doctoral advisor, Professor Jörg Vogel, head of the Institute for Molecular Infection Biology in Würzburg, as well as scientists from Leipzig and Bordeaux, succeeded in proving the existence of small regulatory RNA molecules, known as small RNAs or sRNAs, in Helicobacter pylori for the first time ever.

To achieve this result, the researchers developed a new approach based on a special technique that allows millions of RNA molecules in the cell to be deciphered in parallel. The discovery of more than 60 different sRNAs in Helicobacter was a big surprise to the science world as it had previously been assumed that this bacterium did not possess any regulatory RNAs. What is more, with the help of its new approach, the research group was able to map all the gene start points in the Helicobacter genome for the very first time (Sharma et al., 2010, Nature).

Tasks of small RNA molecules

To put it simply, bacteria use small RNA molecules to control their gene expression and to adapt to changing living conditions or stress conditions. Small RNA molecules usually bind to certain segments in messenger RNAs and thereby influence the synthesis of specific proteins. In so doing, they are able to deactivate or activate genes. However, there are still huge gaps in knowledge in this area: “The functions and mechanisms of most RNAs in Helicobacter and in many other pathogens remain completely unknown,” says Sharma.

This is something that this Doctor of Biology would like to change with her team over the next few years: What functions do the newly discovered sRNAs in Helicobacter possess? Which target genes do they regulate? How are they themselves regulated? And what significance do they hold for the pathogenic potential of the bacterium? Sharma’s team is looking for answers to these questions.

How are they going about this? “We are subjecting the bacterium to different stress or growth conditions and then examining which sRNA molecules increase in number and which do the opposite,” she says. Stress for a bacterium may mean changing living conditions, such as pH fluctuations or temperature changes, a shortage of certain nutrients or even an immune defense attack. The change in sRNA quantities will enable the researchers to draw conclusions about possible target genes or processes that are regulated by the sRNA. Sharma and her colleagues are also generating mutant bacteria in which the corresponding sRNA gene features particularly frequently or particularly rarely and are seeing which proteins or messenger RNAs appear in increased or reduced numbers.

Targets for new therapies

One of the goals of the work is to identify those sRNAs that are responsible for making a bacterium give a person diarrhea or stomach ulcers. “If it is known which sRNAs trigger certain pathologies or play a role in their virulence, they will represent new targets for diagnostics or treatments,” explains Sharma. In this day and age, when more and more strains of bacteria are becoming resistant to the usual antibiotics, new treatments are needed urgently.

Besides the functions of sRNAs, Sharma and her team are also interested in proteins that are involved in a process known as riboregulation. “Helicobacter, like 50 percent of all bacteria, is missing a central RNA-binding protein that the sRNAs of numerous other bacteria need for gene regulation or for their own stability,” says Sharma. Consequently, she and her colleagues are looking for other proteins that could take over this function.

“Our goal is to establish Helicobacter and Campylobacter as new model organisms for riboregulation in pathogenic bacteria,” explains Sharma. Once the scientists have worked out the various mechanisms using Helicobacter and Campylobacter as examples, it will be possible to use this information to understand the virulence mechanisms of other pathogens that follow the same principle.

The Bavarian Academy’s Förderkolleg

In 2010, the Bavarian Academy of Sciences and Humanities founded the Förderkolleg. It admits six excellent young scientists into the program each year. The participants receive 1000 euros a month for at least three years, which they can spend on whatever they want, be this laboratory materials, conference visits or a child minder for their own youngsters.

There are regular meetings intended to promote interdisciplinary scientific exchange, and mentors are on hand to provide the young scientists with help and advice.