Category Archives: Transhuman News

IMAGE:New grants fund research on how the genes and switches in the genome fit together as networks. view more

Credit: Darryl Leja, NHGRI

The National Institutes of Health has awarded grants of more than $28 million aimed at deciphering the language of how and when genes are turned on and off. These awards emanate from the recently launched Genomics of Gene Regulation (GGR) program of the National Human Genome Research Institute (NHGRI), part of NIH.

"There is a growing realization that the ways genes are regulated to work together can be important for understanding disease," said Mike Pazin, Ph.D., a program director in the Functional Analysis Program in NHGRI's Division of Genome Sciences. "The GGR program aims to develop new ways for understanding how the genes and switches in the genome fit together as networks. Such knowledge is important for defining the role of genomic differences in human health and disease."

With these new grants, researchers will study gene networks and pathways in different systems in the body, such as skin, immune cells and lung. The resulting insights into the mechanisms controlling gene expression may ultimately lead to new avenues for developing treatments for diseases affected by faulty gene regulation, such as cancer, diabetes and Parkinson's disease.

Over the past decade, numerous studies have suggested that genomic regions outside of protein-coding regions harbor variants that play a role in disease. Such regions likely contain gene-control elements that are altered by these variants, which increase the risk for a disease.

"Knowing the interconnections of these regulatory elements is critical for understanding the genomic basis of disease," Dr. Pazin said. "We do not have a good way to predict whether particular regulatory elements are turning genes off or activating them, or whether these elements make genes responsive to a condition, such as infection. We expect these new projects will develop better methods to answer these types of questions using genomic data."

Recipients of the new GGR three-year grants (pending available funds) are:

The body's immune system can cause inflammation, which plays a central role in some diseases. The investigators will use a mouse model to study genomic mechanisms underlying immune system activity during inflammation. They will determine what and when genes are turned on and off, and how they are controlled, in the development and activation of two different types of immune cells with opposite functions. One cell type promotes the immune system's response and inflammation; the other dampens these functions.

Researchers will characterize how human lung epithelial cells respond to anti-inflammatory drugs called glucocorticoids (a type of steroid hormone). They will determine what and when genes are turned on and off, and how this process is controlled. They hope to create a model for this type of response, and detail the gene regulation patterns involved. This may allow the researchers to understand how glucocorticoids control both anti-inflammatory and metabolic responses.

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NIH grants aim to decipher the language of gene regulation

Steve Gschmeissner/SPL

Ovarian cancer is one of a few tumour types that will continue to be intensively sequenced after the end of a massive US cancer-genomics effort.

A mammoth US effort to genetically profile 10,000 tumours has officially come to an end. Started in 2006 as a US$100-million pilot, The Cancer Genome Atlas (TCGA) is now the biggest component of the International Cancer Genome Consortium, a collaboration of scientists from 16 nations that has discovered nearly 10million cancer-related mutations.

The question is what to do next. Some researchers want to continue the focus on sequencing; others would rather expand their work to explore how the mutations that have been identified influence the development and progression of cancer.

TCGA should be completed and declared a victory, says Bruce Stillman, president of Cold Spring Harbor Laboratory in New York. There will always be new mutations found that are associated with a particular cancer. The question is: what is the costbenefit ratio?

Stillman was an early advocate for the project, even as some researchers feared that it would drain funds away from individual grants. Initially a three-year project, it was extended for five more years. In 2009, it received an additional $100 million from the US National Institutes of Health plus $175 million from stimulus funding that was intended to spur the US economy during the global economic recession.

The project initially struggled. At the time, the sequencing technology worked only on fresh tissue that had been frozen rapidly. Yet most clinical biopsies are fixed in paraffin and stained for examination by pathologists. Finding and paying for fresh tissue samples became the programmes largest expense, says Louis Staudt, director of the Office for Cancer Genomics at the National Cancer Institute (NCI) in Bethesda, Maryland.

Also a problem was the complexity of the data. Although a few drivers stood out as likely contributors to the development of cancer, most of the mutations formed a bewildering hodgepodge of genetic oddities, with little commonality between tumours. Tests of drugs that targeted the drivers soon revealed another problem: cancers are often quick to become resistant, typically by activating different genes to bypass whatever cellular process is blocked by the treatment.

Despite those difficulties, nearly every aspect of cancer research has benefited from TCGA, says Bert Vogelstein, a cancer geneticist at Johns Hopkins University in Baltimore, Maryland. The data have yielded new ways to classify tumours and pointed to previously unrecognized drug targets and carcinogens. But some researchers think that sequencing still has a lot to offer. In January, a statistical analysis of the mutation data for 21 cancers showed that sequencing still has the potential to find clinically useful mutations (M.S.Lawrence etal. Nature 505, 495501; 2014).

On 2 December, Staudt announced that once TCGA is completed, the NCI will continue to intensively sequence tumours in three cancers: ovarian, colorectal and lung adenocarcinoma. It then plans to evaluate the fruits of this extra effort before deciding whether to add back more cancers.

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End of cancer-genome project prompts rethink

Scientists hope the secret to longevity and disease-resistance could be hidden within the now-sequenced genome of the bowhead whale the longest living mammal. Photo by Olga Shpak

The secret to giving humanity a longer life and protection from age-related illnesses could be hidden within the genome of the longest living mammal.

Scientists have sequenced the complete genome of the bowhead whale, an animal that has been known to live more than 200 years and resist many of the diseases associated with old age. While comparing the creatures genes with other mammals, the research team discovered key alterations related to cell division, DNA repair, cancer, and aging a possible explanation for why the whales not only live so long, but are also resistant to cancer and other diseases in its old age.

My view is that species evolved different tricks to have a longer lifespan, and by discovering the tricks used by the bowhead we may be able to apply those findings to humans in order to fight age-related diseases, Dr. Joo Pedro de Magalhes, senior author of the study published Monday in Cell Reports, said.

The genome data of the whale, the second heaviest whale after the blue whale with around 1,000 times more cells than humans, may also hold clues to explaining physiological differences between animals of different sizes. One example given was that whale cells have a lower metabolic rate compared to smaller mammals, with the explanation possibly being found in a difference within a specific gene related to body temperature regulation.

The complete genome data has been made available by the researchers for free online.

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Can protection from aging be found in a whale genome?

Scientists at the University of Liverpool have sequenced the genome of the bowhead whale, estimated to live for more than 200 years with low incidence of disease.

Published in the journal Cell Reports, the research could offer new insight into how animals and humans could achieve a long and healthy life.

Scientists compared the genome with those from other shorter-lived mammals to discover genetic differences unique to the bowhead whale.

It is thought that large mammals, such as whales, with over 1000 times more cells than humans, have a lower risk of developing cancer, suggesting that these creatures have natural mechanisms that can suppress disease more effectively than those of other animals.

Sequencing of the bowhead whale showed changes in genetic information that related to cell division, DNA repair, disease and ageing that with further analysis, could help inform future studies in longevity and cancer resistance.

Dr Joo Pedro de Magalhes, from the University of Liverpool's Institute of Integrative Biology, explains: "Our understanding of species' differences in longevity is very poor, and thus our findings provide novel candidate genes for future studies.

"We believe that different species evolved different 'tricks' to have a long lifespan, and by discovering those used by the bowhead whale we may be able to apply these findings to humans in order to fight age-related diseases."

The research may also provide clues into why there is significant variance in the size of some mammals.

Dr Magalhes added: "The bowhead's genome is the first among large whales to be sequenced, so this new information may help reveal physiological adaptations related to size that we have not been able to study in any great detail before.

"Whale cells have a much lower metabolic rate than those of smaller mammals, and we found changes in one specific gene involved in thermoregulation (UCP1) that may be related to metabolic differences in whale cells. This might allow us to see how and why bowhead whales and other similar creatures have sustained such an enormous size."

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Scientists sequence genome of longest-lived mammal