Kangaroo Genome Mapped

Kangaroo Genome Mapped
Tuesday, 18 November 2008

Australian researchers will today launch the world first detailed map of the kangaroo genome, completing the first phase of the kangaroo genomics project.

Researchers at the ARC Centre of Excellence for Kangaroo Genomics (KanGO), including University of Melbourne, ANU, WEHI, University of Sydney, University of NSW and the Australian Genome Research Foundation (AGRF) have built a framework to assemble the genome of a model kangaroo, the tammar wallaby.

"A good map is crucial for finding our way around a new genome," said KanGO Director Prof. Jenny Graves, who divides her time between ANU and University of Melbourne.

"It enables us to explore how the genome of mammals - including humans - is organized, how it functions, and how it evolved."

"Now the world can use information on kangaroo genes and sequences to explore how mammals develop and function," she said.

DNA sequence obtained by the Australian Genome Research Facility (AGRF) with funding from the Victorian government will be arranged using the genome map.

Researchers say the international race to sequence the genomes of significant species is driven by the power of genome comparisons – particularly of species that are distantly related – to reveal secrets of the genome in humans, as well as other mammals.

"Australia's weird and wonderful animals are making crucial contributions," Professor Graves said.

"The kangaroo has helped to consolidate Australia's reputation in this important genomics era," she said.

Graves says genomic information is extremely powerful. She says KanGO researchers used the kangaroo genome map to solve fundamental genetic puzzles, for instance discovering the gene that controls the sex of a baby, and overturning theories of the origin of our blood proteins.

The map and sequence will open up new areas of research into how genes are turned on and off during development of all mammals.

"Kangaroos are a marvellous model for studying human development and reproduction because they are born very early and complete much of their development in the pouch - rather than the womb," said Laureate Professor Marilyn Renfree of the University of Melbourne's Zoology Department, who takes over as KanGO Director today.

"This makes them a powerful tool for studying the genes and hormones involved in mammalian reproduction and development."

Professor Graves says that access to the next generation sequencing technologies will mean that the wealth of genetic information in Australia's native flora and fauna can now be tapped into.

"This will provide a depth of understanding never thought possible until recently and lead to new and exciting applications in the field of biotechnology."
.........


ZenMaster

---

For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/ and
http://www.geocities.com/giantfideli/index.html

---

‘Orphan’ Genes Importance in Evolution

‘Orphan’ Genes Importance in Evolution
Tuesday, 18 November 2008

Closely related animal species share most of their genes and look almost identical. However, minor morphological differences allow us to tell them apart. What is the genetic basis for these differences?

Often, the explanation is provided by minor changes in spatial and temporal activity of transcription factors - "regulator" genes that are conserved throughout the animal kingdom. However, every group of animals also possesses a small proportion of genes, which are, in contrary, extremely variable among closely related species or even unique. For example, a gene may be present in one species or animal group, but not in any other. Such genes are referred to as "novel," "orphan" or "taxonomically restricted". Their function and origin are often obscure. What are these genes needed for?

A new paper, published in this week's issue of the online open access journal, PLoS Biology, explores this question in the freshwater polyp Hydra, which belongs to the same branch of the evolutionary tree as jelly fish. These animals are small (several mm long), predatory creatures, with a tube like body-form that ends in a mouth surrounded by mobile tentacles. They are of particular interest to scientists for their regenerative properties, and because they appear to be biologically immortal; not undergoing the aging process that affects all other known animals.

In this paper, a team of scientists from the Christian-Albrechts-Universität zu Kiel in Germany, used transgenic polyps to uncover the role of "orphan" genes in these morphologically-simple animals. The work, led by Thomas Bosch reports that a family of "novel" genes is responsible for morphological differences between two closely related species of fresh water polyps called Hydra. Their most remarkable finding is that a secreted protein, encoded by "novel" gene Hym301, controls the pattern in which the tentacles in Hydra develop.

"We knew that these genes were important, but it was in no sense simple to demonstrate that," says Konstantin Khalturin, first author of the PLoS Biology paper.

---

A freshwater polyp Hydra and its tentacles during bud formation.

---

In one species, Hydra oligactis, emergence of its tentacles during bud formation is not synchronised; in Hydra vulgaris all five tentacles develop simultaneously and symmetrically; in Hydra vulgaris polyps genetically altered to produce large amounts of protein from the “orphan gene” Hym301, tentacles are formed in an irregular and asymmetric pattern.

The data indicate that "novel" genes are involved in generation of novel morphological features that characterise different species, thus pointing the way to a new, more complete understanding of how evolution works at the level of a particular group of animals. Emergence of "novel" genes may reflect evolutionary processes, which allow animals to adapt in the best way to changing environmental conditions and new habitats.

Reference:
A novel gene family controls species-specific morphological traits in Hydra
Konstantin Khalturin, Friederike Anton-Erxleben, Sylvia Sassmann, Jörg Wittlieb, Georg Hemmrich, Thomas C. G. Bosch
PLoS Biol 6(11)(2008): e278 doi:10.1371/journal.pbio.0060278
.........


ZenMaster

---

For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/ and
http://www.geocities.com/giantfideli/index.html

---

US Scientists Self-censor During Bush Administration

US Scientists Self-censor During Bush Administration
Tuesday, 18 November 2008

A survey of scientists whose studies became the focus of a public debate about NIH grant funding has found that many of them engaged in self-censorship as a result of the controversy. The study, published in the open access journal PLoS Medicine, found that following the criticism of their research, scientists removed politically sensitive language from grant applications and stopped studying certain topics. These self-censorship tactics were employed despite the fact that all of the criticised studies — most of which investigated sexual behaviour, drug-use, and other HIV-related questions — were defended in an NIH internal review and retained their funding.

Joanna Kempner of Rutgers University in New Jersey surveyed the researchers who were the subject of a debate in the US in July 2003, which began when a Congressional Representative proposed an amendment to rescind five NIH grants after publicly criticising the studies as "less worthy of taxpayer funding" than research into "devastating diseases." The amendment failed to pass but the controversy resulted in the internal review of more than 250 grants by the NIH, which concluded that each study was scientifically sound.

After conducting in-depth interviews with thirty researchers whose funding was reviewed, Kempner surveyed the principal investigators of all the studies. Only a third of the 82 respondents felt they were less likely to receive funding from the NIH in the future, but a majority reported undertaking strategies designed to disguise the most controversial aspects of their research. Half (51%) said they removed potential "red flag" words from the titles and abstracts of their grant submissions, including the words gay, lesbian, homophobia, anal sex, needle-exchange, and AIDS. Kemper reports that one interviewee said "I do not study sex workers, I study 'women at risk.'"

Almost a quarter of the researchers had either reframed their studies to avoid research on marginalized or stigmatized populations or had chosen to drop studies that were thought to be political sensitive, such as those on sexual orientation, abortion, childhood sexual abuse, and condom use. The survey also found that four of the principal investigators had made career changes and left academia as a result of the controversy.

Joanna Kempner stresses that the controversy also galvanized sections of the research community with 10% of respondents reporting a strengthened commitment to see their research completed, including those who had reported self-censorship practices. She says that the findings are a powerful example of how the political environment can shape what scientists chose not to study.

Reference:
The chilling effect: How do researchers react to controversy?
Kempner J
PLoS Med 5(11): e222. doi:10.1371/journal.pmed.0050222
.........


ZenMaster

---

For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/ and
http://www.geocities.com/giantfideli/index.html

---

Cellular Damage in Huntington's Disease

New clues emerge from study
Monday, 17 November 2008

"Huntington's disease presents an ideal vantage point to study neurodegenerative disease, because we know the misfolded protein that's responsible," says Martin Duennwald, formerly a postdoctoral researcher in the lab of Whitehead Institute for Biomedical Research member Susan Lindquist.

"But we don't understand how this protein causes cellular damage and death for the neurons that are affected."

In a study published in Genes & Development online on November 17, however, Duennwald and Lindquist report the discovery of a mechanism driven by the misfolded proteins that could be one early trigger for cell death.

In the U.S., about 1 in 20,000 people suffers from Huntington's. Better understanding of the cellular toxicity may allow new therapies for this fatal and incurable disorder.

"This is a diabolical disease, because the misfolded protein interacts with and probably traps many other proteins in the cell," notes Lindquist, who is also a Howard Hughes Medical Institute investigator and a professor of biology at Massachusetts Institute of Technology.

Scientists have long known that a single mutated gene that creates proteins with abnormally long repeats of the amino acid glutamine (“Q”) drives Huntington’s. In certain neurons, these "polyQ-expanded" proteins misfold and clump together, damaging and eventually killing the cells.

But the steps that kick off the process of cell damage and death have remained a mystery, remarks Duennwald, now a principal scientist at Boston Biomedical Research Institute in Watertown, Mass.

In the study, Duennwald first examined what makes polyQ-expanded proteins toxic in yeast. He then performed similar experiments in two kinds of mammalian cells — rat cells that model neurons and mouse striated cells (from the part of the brain most afflicted in Huntington's).

He found that cells generated with polyQ-expanded fragments quickly showed problems with proteins that had been marked for degradation in the endoplasmic reticulum (ER, a cell component that folds and finalizes proteins). Such proteins were not expelled for tagging and degradation in the cytosol, the intracellular fluid, outside the ER.

"With no garbage disposal, all of a sudden the ER is flooded with proteins that need to be degraded," he says. This breakdown in protein quality control may lead toward cell damage and death.

"We were quite surprised because the ER didn't seem to have any connection with the misfolded proteins in the cytosol," Duennwald adds.

"This study tells us to investigate cellular pathways beyond the usual suspects."

He went on to uncover the basis for this breakdown: The polyQ-expanded fragments glom onto the key VCP/Npl4/Ufd1 protein complex that aids in the transport and degradation of the proteins that flunk quality control in the ER. When Duennwald genetically modified cells to over-express two crucial proteins in the protein complex, the toxic effect dropped.

Additionally, his experiments showed that polyQ-expanded proteins avoid a main method by which cells deal with misfolded proteins. Generally, a class of proteins called "chaperone" or "heat shock" proteins move in and either help the misfolded proteins assume their normal shape or help to get rid of them.

"Amazingly, polyQ-expanded proteins don't elicit the heat shock response, and that might contribute to their toxicity," Duennwald says.

Such findings may help in eventually treating the disease. The research suggests that activating the cell's protein quality control mechanisms may provide novel and effective strategies for combating Huntington's and other illnesses driven by polyQ-expanded proteins.

Reference:
Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity
Martin L. Duennwald and Susan Lindquist
Genes & Development, December 2008
.........


ZenMaster

---

For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/ and
http://www.geocities.com/giantfideli/index.html

---