Antibacterial drugs

Type II fatty acid synthesis is not a suitable antibiotic target for Gram-positive pathogens Brinster, S. et al. Nature 458, 83–86 (2009)

This paper showed that the strategy for antibiotic development based on reportedly essential type II fatty acid synthesis (FASII) pathway targets is flawed. The authors found that Gram-positive pathogens — such as streptococci, pneumococci, enterococci and staphylococci — overcame drug-induced FASII pathway inhibition when supplied with exogenous fatty acids. Moreover, the FASII target enzymes were not required during Streptococcus agalactiae septicaemic infection in vivo. These findings question the use of FASII-based antimicrobials for treating sepsis caused by Gram-positive pathogens.

Obesity and diabetes

Molecular therapy of obesity and diabetes by a physiological autoregulatory approach Cao, L. et al. Nature Med. 15, 447–454 (2009)

The authors of this study investigated the therapeutic efficacy of brain-derived neurotrophic factor (BDNF) — a key regulator of energy balance — delivered by gene transfer in mouse models of obesity and diabetes. They developed a molecular autoregulatory system that was responsive to BDNF-induced physiological changes so that, as body weight decreased and agouti-related protein expression was induced, BDNF microRNA expression was activated, inhibiting transgene expression. In contrast to the progressive weight loss that is associated with a non-regulated gene transfer approach, this method led to a sustainable plateau of body weight following weight loss.

Vaccine design

Instant immunity through chemically programmable vaccination and covalent self-assembly Popkov, M. T. et al. Proc. Natl Acad. Sci. USA 106, 4378–4383 (2009)

Popkov and colleagues used reactive immunization to create a reservoir of covalent polyclonal antibodies in mice. Following administration of designed integrin αvβ3 and αvβ5 adapter ligands, polyclonal antibodies self-assembled with these ligands and the animals mounted an instant, chemically programmed, polyclonal response against syngeneic tumours. There was a decrease in tumour growth, showing that elements of active and passive immunization can be combined to create an effective chemistry-driven approach to vaccine design.

Stem cells

A small molecule that directs differentiation of human ESCs into the pancreatic lineage Chen, S. et al. Nature Chem. Biol. 5, 258–265 (2009)

Differentiation of human embryonic stem cells (hESCs) is currently achieved by co-culturing the cells with other cell types and/or growth factors. As an alternative approach, Chen and colleagues developed a high-content screen to identify small molecules that increased the number of pancreatic progenitor cells derived from hESCs. One compound, (–)–indolactam V, worked by inducing pancreatic progenitors from definitive endoderm and activating protein kinase C. Moreover, indolactam-treated cells were able to form mature pancreatic cells.