Targeting iron assimilation to develop new antibacterials

HIV-1 Integrase Inhibitor-Inspired Antibacterials Targeting Isoprenoid Biosynthesis.

We report the discovery of antibacterial leads, keto- and diketo-acids, targeting two prenyl transferases: undecaprenyl diphosphate synthase (UPPS) and dehydrosqualene synthase (CrtM). The leads were suggested by the observation that keto- and diketo-acids bind to the active site Mg(2+)/Asp domain in HIV-1 integrase, and similar domains are present in prenyl transferases. We report the x-ray cr...

Targeting Bacterial Persistence to Develop Therapeutics Against Infectious Disease

Iron targeting to mitochondria in erythroid cells.

Immature erythroid cells have an exceptionally high capacity to synthesize haem that is, at least in part, the result of the unique control of iron metabolism in these cells. In erythroid cells the vast majority of Fe released from endosomes must cross both the outer and the inner mitochondrial membranes to reach ferrochelatase, which inserts Fe into protoporphyrin IX. Based on the fact that Fe...

Antibody engineering to develop new antirheumatic therapies

There has been a therapeutic revolution in rheumatology over the past 15 years, characterised by a move away from oral immuno-suppressive drugs toward parenteral targeted biological therapies. The potency and relative safety of the newer agents has facilitated a more aggressive approach to treatment, with many more patients achieving disease remission. There is even a prevailing sense that dise...

Using New Standards to Develop IC Ontologies

In this paper we describe recent work in adapting various new OWL and ontology standards to ontology development for the IC and DoD. We present work done to adapt the Universal Core Semantic Layer (UCore SL) standard ontology to support intelligence analysts. We show how new features in the OWL 2 standard can be used to make such ontologies simpler and more readable, and how they facilitate mod...