Seminar by Professor Paul Thornalley and Dr Chrystala Constantinidou, Division of Biomedical Sciences, Warwick Medical School
When the sweet turns nasty! Prerequisites, mechanisms and new therapeutics for chronic vascular complications of diabetes
Chronic vascular complications are the major cause of morbidity and premature mortality in the diabetic patient population. These are: microvascular complications – nephropathy, retinopathy and neuropathy; and macrovascular complications - coronary artery disease, peripheral arterial disease and stroke. Current treatment is ineffective and new options are limited. For example, on-treatment mortality of diabetic patients with nephropathy is higher than for cancer and the last clinical trials leading to licensed new drugs for diabetic nephropathy reported 17 years ago.
Dysregulation and misuse of glucose in peripheral sites in hyperglycemia drives the development of diabetic vascular complications. The seminar will address recent advances that have identified the key prerequisites for cell and tissue vulnerability to the chronic damaging effects of hyperglycemia, the mechanisms involved and a new approach to therapy in clinical evaluation – Glyoxalase 1 inducers.
Flagella assembly and regulation in polar bacteria
Flagella are complex structures formed by up to 100 different proteins. The assembly of the proteins follows a specific order, beginning from the inner end of the construction (cytoplasm and inner membrane) and finishing at the outer end of the organelle outside the bacterium. Flagella-gene expression is mediated in a hierarchical manner. Adding to the complexity are the diverse patterns and numbers of flagella different bacterial species possess. For pathogenic bacteria such as Campylobacter jejuni, flagellar motility and chemotaxis play key roles in intestinal colonisation, invasion of epithelial cells, biofilm formation and protein secretion. A number of genes of unknown function have been identified as crucial for the correct assembly of the flagellar structures in C. jejuni and other polar bacteria. Studies on one such gene, flhF, have provided us with novel insights into the regulation of flagellar biogenesis.