HIV study identifies key cellular defence mechanism

Scientists have moved a step closer to understanding how one of our body’s own proteins helps stop the human immunodeficiency virus (HIV-1) in its tracks.

The study led by Michelle Webb, carried out by researchers at The University of Manchester and the Medical Research Council’s National Institute for Medical Research and published in Nature, provides a blueprint for the design of new drugs to treat HIV infection, say the researchers.

Scientists in the United States and France recently discovered that a protein named SAMHD1 was able to prevent HIV replicating in a group of white blood cells called myeloid cells. Now, crucially, the teams from Manchester and the MRC have shown how SAMHD1 prevents the virus from replicating itself within these cells, opening up the possibility of creating drugs that imitate this biological process to prevent HIV replicating in the sentinel cells of the immune system.

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Full paper: Nature

Bacteria shed light on new drug targets for inherited cancers

Prof David Leys and colleagues at the University of Manchester’s Paterson Institute for Cancer Research have succeeded in purifying a protein found in bacteria that could reveal new drug targets for inherited breast and ovarian cancers as well as other cancers linked to DNA repair faults. The team are the first to decipher the structure of a protein called PARG – which plays an important role in DNA repair and acts in the same pathway as PARP. Read more

The study is published in the journal Nature - click here for Full article

Scientists at The University of Manchester have discovered a way of speeding up the creation of perfect drug combinations, which could help patients recovering from critical health problems such as stroke, heart attacks and cancer.

The researchers found a way of identifying ideal drug combinations from billions of others which would prevent inflammation from occurring.

The findings, published in Nature Chemical Biology, could be the first step in the development of new drug combinations to combat severe diseases and conditions. Read more

Efficient discovery of anti-inflammatory small molecule combinations using evolutionary computing

Nature Chemical Biology, 2011, 7:902-908.Small BG, McColl BW, Allmendinger R, Pahle J, Lopez-Castejon G, Rothwell NJ, Knowles J, Mendes P, Brough D, Kell DB,

In this study Small et al optimised drug cocktails to inhibit a major inflammatory reaction; the expression of the key pro-inflammatory cytokine interleukin-1beta. The aim of this study was to investigating the effects of low dose drug combinations on inflammation. Using drugs, or reagents, in combination revealed synergy and improved the inhibitory effects of reagents at lower concentrations than were observed when the reagents were used singly. To overcome the experimentally unfeasible task of testing all reagents in combination from a library containing 30 reagents, Small et al used a multi-objective evolutionary algorithm to optimise the reagent combinations over successive generations. Shown is the synergy in inhibiting the expression of interleukin-1beta between two of the most effective reagents tested; a P38 MAPK inhibitor, and a NF-kB inhibitor. Interleukin-1beta is central to the pathogenesis of diverse and major human diseases and optimising drug cocktails in this way could lead to the development of new anti-inflammatory therapies. Paper