Making new pharmacological tools ™ to explore individual genes is an enormous challenge, but vital for public health. Testing specific genes gives us fundamental knowledge on how we could predict and prevent disease, said Professor David Beech. It also plays the crucial role of confirming valid gene targets ™ before the pharmaceuticals industry carries out complex and expensive research and development. The problem is that tools which hit just one gene-product - or protein - are extremely rare.
The University ™s 5m integrative membrane biology centre, which opened in October, has become a hub for research on ion channels “ doors ™ controlling the movement of ions including sodium and calcium into the body ™s cells. Abnormalities in these channels cause many diseases, so they are often the focus of drugs.
Professor Beech has developed a simple method for blocking the function of these channels by targeting the E3 region, important because it is accessible to antibodies introduced from outside the cells, making it an ideal drug target. By blocking one particular channel in this region, we can see how calcium movement through this protein impacts on vascular disease, said Professor Beech.
Professor Beech ™s findings were published in a prestigious research article in Nature Biotechnology last month. The research was funded by the Wellcome Trust and the British Heart Foundation.
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Fredricks and colleagues postulated that one reason for BV's persistent mystery is that scientists haven't identified the total community of bacteria that causes it. Indeed, the study found that most of the bacterial species detected in vaginal fluid are missed with conventional cultivation methods. The researchers catalogued a total of 35 bacterial species associated with BV, doubling the known species. Nineteen appear to be novel species, the study reported. The study identified three new strains, members of the Clostridium phylum, which researchers named BV-associative bacterium # 1, 2 and 3. They had specificities of 95 percent to 98 percent, meaning their detection in vaginal fluid reliably predicted the presence of BV. On the other hand, not all women with BV harbored these novel Clostridium-like bacteria.
"Numerous bacterial genera identified in this study have not, to our knowledge, been previously detected in the vaginal milieu with the use of cultivation methods," researchers said.
Rather than grow bacteria in a Petri dish -the standard identification method -Fredericks harvested DNA from bacteria, cloned segments of the DNA and used polymerase chain reaction (PCR) assays to analyze and sequence the segments. PCR analysis has a high degree of sensitivity and specificity. What made this possible is that every bacterium has the 16S ribosomal RNA gene, the gene that codes for ribosomes, which are the protein synthesizing machinery of cells.
"The 16S ribosomal RNA gene is unique for each different species of bacterium," said Fredricks. "By knowing the sequence of the gene you can identify the bacterium. We get a sort of molecular bar code." With these read outs, researchers went online to the GenBank database operated by the National Institutes of Health and looked for matches among the bacterial strains catalogued there.
Now that a more complete catalogue of bacterial strains has been assembled, Fredricks said work can begin looking for specific associations between individual species and the more adverse health problems linked to BV.
Fredricks said the larger lesson from PCR analysis is just how complex the human microbial ecosystem is. Other syndromes being investigated using PCR include ulcerative colitis, Crohn's disease, pneumonia and meningitis.
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