Wellcome Trust Research Round-up: 13/10/14

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

Identifying the genetic factors of height is a tall order

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Clik here to view.An international collaboration of scientists has identified a fifth of the genetic factors that cause height to vary between individuals.

A study which examined data on DNA from more than 250,000 people, published in Nature Genetics, roughly doubles the number of known genome regions involved in height to more than 400. It also revealed that more than half of the factors involved in determining height are explained by simple common genetic variation – the sort of genetic variation that exists in more than 1 in 10 people.

The research team checked more than 2 million common genetic factors – those shared by at least five per cent of participants. From this they found 697 genetic variants in 424 regions of the genome that are related to height. The findings represent a massive stride forward in an area of research in which virtually nothing was known as recently as 2007.

Professor Tim Frayling from the University of Exeter Medical School, who oversaw the study, said: “It’s common knowledge that people born to tall parents are more likely to be tall themselves. Most of this is down to the variations in our DNA sequence that we inherit from our parents – the different versions of all our genes. We have now identified nearly 700 genetic variants that are involved in determining height.”

He added: “[This research] is also a step forward towards a test that may reassure parents worried that their child is not growing as well as they’d hoped – most of these children have probably simply inherited a big batch of “short genes”.

The collaboration, aptly named the GIANT consortium, is co-led by the University of Exeter Medical School and part-funded by the Wellcome Trust.

Watching molecules ‘wiggle’

A new crystallographic technique developed is set to transform scientists’ ability to observe how molecules work.

A research paper, published in the journal Nature Methods, describes a new way of doing time-resolved crystallography, a method that researchers use to observe changes within the structure of molecules.

The new method will allow researchers across the world to carry out dynamic crystallography and is likely to provide a major boost in areas of research that rely on understanding how molecules work, such as the development of novel smart materials or new drugs.

Understanding how structure and dynamics are linked to function is key to designing better medicines that are targeted at specific states of molecules, helping to avoid unwanted side effects.

“A time-resolved structure is a bit like having a movie for crystallographers,” said Professor Arwen Pearson, who led the team at the University of Leeds. “Life wiggles. It moves about and, to understand it, you need to be able to see how biological structures move at the atomic scale. This breakthrough allows us to do that.

The research was funded by the Wellcome Trust and was conducted at the University of Leeds and the Diamond Light Source.

First pictures show how BRCA2 protein works to repair damaged DNA

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Mutations in the gene that encodes BRCA2 are well known for raising the risk of breast cancer and other cancers. Although the protein was known to be involved in DNA repair, its shape and mechanism have been unclear, making it impossible to target with therapies.

Researchers at Imperial College London and the Cancer Research UK London Research Institute (LRI) purified the protein and used electron microscopy to reveal its structure and how it interacts with other proteins and DNA. The results are published in Nature Structural and Molecular Biology.

Around 1 in 1000 people in the UK have a mutation in the BRCA2 gene. The lifetime risk of breast cancer for women with BRCA2 mutations is 40 to 85 per cent, depending on the mutation, compared with around 12 per cent for the general population. Many women who test positive for BRCA1 and BRCA2 mutations choose to undergo surgery to reduce their risk of breast cancer. Mutations can also raise the risk of other cancers, such as ovarian, prostate and pancreatic cancer.

The BRCA1 and BRCA2 genes encode proteins involved in DNA repair. The DNA in our cells undergoes damage thousands of times a day, caused by toxic chemicals, metabolic by-products and ultraviolet radiation. Repair mechanisms correct most of this damage, but unrepaired damage can lead to cancer.

“This study improves our understanding of a fundamental cause of cancer,” said Professor Xiaodong Zhang, a Wellcome Trust Senior Investigator, who led the research along with Dr Stephen West at the LRI. “It’s our first view of how the protein looks and how it works, and it gives us a platform to design new experiments to probe its mechanism in greater detail.”

In other news…

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Clik here to view.Wellcome Trust governor Professor Kay Davies and Wellcome Trust Senior Fellow Professor Jane Clarke have been shortlisted for the 2014 WISE Lifetime Achievement Award and WISE Champion Award respectively. WISE (Women in to Science and Engineering), is an organisation whose mission is to increase the gender balance in the UK’s STEM workforce.

The Wellcome Trust is collaborating with Merck Serono (the biopharmaceutical division of Merck) and the Institute of Cancer Research to identify inhibitors of tankyrase, an enzyme of the poly (ADP-ribose) polymerase family, with the goal of bringing a new cancer therapeutic drug to patients. The agreement follows on from an existing drug discovery program at the ICR, which supported by a Seeding Drug Discovery Award.

Image credit: Kay Davies – Anne-Katrin Purkiss, Wellcome Images

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