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Wellcome Trust Research Round-up: 30.03.15

30 Mar, 2015

Our fortnightly round-up of news from the Wellcome Trust community…

New insight into TB immune evasion

B0004331 DNA sequenceA new version of a gene, that may help to explain why some people are more susceptible to TB than others, has been identified in a Wellcome Trust-funded study.

Although TB infects an estimated two billion people worldwide, only a small proportion of these cases ever progress from the latent (without symptoms) phase, to the active form of the disease. Recent studies have highlighted the role of a person’s DNA in determining whether they become infected, and on the progression of the disease.

By analysing entire genomes, the researchers identified a new version of a gene, present on chromosome eight, called ASAP1. This gene holds the genetic instructions for a protein that is highly expressed in certain specialised cells of the immune system. Following infection with TB, ASAP1 expression is reduced, however researchers found that patients with a particular variant of the gene showed a more marked reduction.

The reduction in ASAP1 protein affects the mobility of immune cells, which slows their migration around a patient’s body. The TB bacterium can more easily evade these slow-moving cells, contributing to increased susceptibility to TB for patients carrying this gene variant.

“Our study provides a new insight into biological mechanisms of TB,” explained Dr Sergey Nejentsev, Wellcome Trust Senior Research Fellow from the University of Cambridge, who led the research. “TB is a major global health problem and the threat of drug-resistance means that we urgently need to develop new ways of fighting back. In future, it may be possible to target immune pathways that involve ASAP1 to design efficient vaccines for TB prevention.”

This study was originally published in Nature Genetics.

Vitamin A helps keep the doctor away

4398689374_82c847830c_zWe may be one step closer to understanding the cause of certain autoimmune conditions, with a new study identifying a key role for Retinoic Acid, a type of vitamin A, in regulating T cells.

Wellcome Trust-funded researchers have found that retinoic acid can ensure T cells change to become a certain type of T helper cell, the Th1 cells, rather than Th17 cells, which have been implicated in several human autoimmune diseases.

T Helper cells (or CD4+ cells) are a subset of T Lymphocytes that, as the name suggests, assist other immunological processes. Upon activation the helper cells differentiate further into several subtypes, each of which helps to activate a different type of immune response.

During the initial stages of T cell priming, it is important for them to be able to switch fate between the subclasses. However at later stages this plasticity is dangerous, and certain types of Th17 cells are implicated in human autoimmune diseases including rheumatoid arthritis and inflammatory bowel disease.

Researchers found that the binding of retinoic acid to its receptor enhances expression of genes required for Th1 type cells, while repressing genes that regulate the Th17 cell fate. The research was published in Immunity.

By identifying a point at which improper regulation of T-cell differentiation could occur, this work has highlighted a potential pathway for intervention in certain autoimmune diseases.

Breastfeeding linked to higher adult IQ

11581822006_ed46bb8777_mA new long-term study has identified an association between the length of time a child is breastfed and IQ, schooling and earnings in adult life.

The Wellcome Trust-funded study, published in the Lancet, involved nearly 3500 babies born in Pelotas, Brazil in 1982 and is one of the first studies to look in-depth at the long-term benefits of breastfeeding. Information on breastfeeding habits was collected in early childhood and then 30 years later participants were given an IQ test.

Researchers found that with all durations of breastfeeding there was an increase in IQ, schooling and adult earnings, but that this increase was significantly greater the longer the child was breastfed for. For example, a child who had been breastfed for at least a year gained a full four IQ points and had 0.9 years more schooling at the age of 30, compared to those breastfed for less than one month.

Studies into the benefits of breastfeeding have often been criticised for failing to disentangle breastfeeding from socioeconomic status, but the Wellcome-funded study addresses this for the first time. In the populations studied breastfeeding was equally distributed across social classes.

Lead author Dr Bernardo Lessa Horta said: “The effect of breastfeeding on brain development and child intelligence is well established, but whether these effects persist into adulthood is less clear. Our study provides the first evidence that prolonged breastfeeding not only increases intelligence until at least the age of 30 years but also has an impact both at an individual and societal level by improving educational attainment and earning ability”.

Bovine bugs hold clue to controlling infectious disease

L0034933 A cow named "Vaccination"Parasites found in African cattle could offer a new insight into ways of combatting serious parasitic diseases in humans, including malaria.

A team funded by the Wellcome Trust has found that cows can be protected from parasites that cause deadly diseases if they have been infected with a closely related, but milder species of the parasite earlier in life.

The health of 500 Kenyan calves was tracked from birth, including whether they had been infected by any viruses, bacteria or parasites. Deaths from East Coast Fever, the biggest killer of African cattle, dropped by 89% in calves that were already infected by another species of parasite that did not cause disease.

As well as the clear economic benefits to African farmers that vaccinating calves with benign parasites could bring, this research could lead to future approaches to human diseases. The study, published in Science Advances, suggests that people infected with a parasite that causes severe malaria may be more likely to survive if they are also infected by a less aggressive species at the same time.

Professor Mark Woolhouse, of the University of Edinburgh’s Centre for Immunity, Infection and Evolution, said: “This discovery suggests a completely new way to control a devastating disease in cattle, while reducing the use of antibiotics and environmentally damaging pesticides at the same time. It may also provide clues to new ways of combatting human diseases such as malaria.”

In Other News

The list of recipients of the Sir Henry Dale Fellowship has just been announced. A collaboration between the Wellcome Trust and the Royal Society, the fellowships recognise outstanding post-doctoral scientists who want to address major biomedical questions. This year’s recipients will be working on a variety subjects including liver regeneration, autism spectrum disorders and female infertility.

Peter Piot has been awarded the Gairdner Foundation’s 2015 Global Health prize. The Director of the London School of Hygiene and Tropical Medicine, and a great friend of the Trust, was recognised for his part in the co-discovery of the Ebola virus and his many contributions to the HIV/AIDS field.

PhD student Oliver Britton, working with Wellcome Trust Senior Research Fellow Professor Blanca Rodriguez, at the University of Oxford, has won the international NC3Rs prize with his research into a new approach to computer modelling of cardiac electrophysiology. It is the first time the prize, which recognises work that has the potential to reduce the number of animals used in research, has been awarded to a PhD student since the prize began in 2005.

There are just a few days left to apply for the British Science Association’s Media Fellowship. This unique opportunity gives practising scientists, clinicians and engineers the chance to spend three to six weeks working in a major news outlet. The application deadline for this year’s fellowship is 3rd April 2015.

Image credits: (From top to bottom) Kate Whitley – Wellcome Images; Vitamin A by Colin Dunn, via Flickr CC-BY; Breastfeeding welcome here, by Leo Reynolds on Flickr – CC-BY-NC-SA, A cow named “Vaccination” – Wellcome Library, London.

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