Scientists discover switch to speed up stem cell production

2011-05-19

(Press-News.org) A team of scientists from Genome Institute of Singapore (GIS) of the Agency for Science, Technology and Research (A*STAR) have shown how proteins involved in controlling genes work together to carry out their functions in stem cells and demonstrated for the very first time, how they can change interaction partners to make other types of cells. The work highlighted the collaborative nature of modern biology in which techniques and knowledge from bioinformatics analysis, structural biology, biochemistry and stem cell molecular biology were used together to find the specific amino acid within the protein that facilitated the molecular switch between stem cells and other types of cells. This discovery, published in the journal Stem Cells, has implications for generating stem cells more efficiently for biomedical applications and could help facilitate the development of treatments for diseases such as diabetes, Parkinson's disease, and Huntington's disease.

Dr Larry Stanton, Deputy Director for Research Affairs and Senior Group Leader of the Stem Cell and Developmental Biology department at GIS, together with Dr Prasanna Kolatkar, Dr Ralf Jauch, Dr Irene Aksoy and other colleagues from GIS, were able to take a protein, Sox17, which normally makes gut cells, and convert it into making stem cells by changing a single amino acid. Significantly, the "new" Sox17 protein was able to make stem cells at five times the normal rate. The scientists were also able to take Sox2, a protein that normally creates stem cells and a close relative of Sox17, and convert it into making gut cells.

Dr Larry Stanton, one of the co-leaders of the project, said, "This research is a modification of the old theory that there are few native transcription factors which can help to make induced pluripotent stem cells. We show that one can take a transcription factor without IPS cell forming activity and in fact make it much more potent."

Dr Prasanna Kolatkar, Dr Stanton's partner in the research, "This is the first time inter-conversion of cell developmental programs has been demonstrated. Furthermore, this functional switch change was implemented by mutating a single amino acid thus showing the atomic level of understanding of the mechanism. There are many groups worldwide working on aspects of transcription factors and stem cells, as well as other groups focusing on the biochemistry and structural biology of transcription factors. What distinguishes our group is the unique integrative and collaborative science at GIS enabling us to bridge the gap between the two disciplines to study the science of transcription factors in stem cells."

"This is an elegant study combining a range of approaches from bioinformatics to in vivo studies to switch protein functions with a tweak of just a single amino acid," said Dr Ian Chambers, Professor of Pluripotent Stem Cell Biology at the University of Edinburgh. "By carefully comparing the biochemical properties of one of the keepers of pluripotent identity, Sox2 and the related pluripotency destroying factor, Sox17, Jauch and co-workers have made the stunning discovery that these divergent biological functions are caused largely by the identity of a single amino acid side chain in the DNA binding domain of the Sox proteins that interfaces with the transcription factor Oct4 and determines the selectivity of the Oct4/Sox binary complex for DNA. This is precisely the type of analysis that will be required to obtain the deep understanding of control of stem cell identity that is absolutely essential if we are to properly and safely use pluripotent stem cells for regenerative strategies."

Dr Alan Colman, Executive Director of the Singapore Stem Cell Consortium at the Institute of Medical Biology, A*STAR, said, "Transcription factor (TFs) interactions with genomic DNA are one of the main elements that define cell identity during development and in adult organisms. One of the mysteries of the field is how structurally similar TFs can have very diverse effects. In a remarkable piece of work that combines diverse techniques such as X-ray crystallography, gene mutagenesis and functional analysis, my colleagues at the A*STAR Genome Institute and the Nanyang Technological University show that the change of a single amino acid can cause TFs to assume a completely different functional character."

Continued Dr Colman, "This piece of truly elegant and insightful work is evidence of what can happen when talent from diverse fields come together to achieve breakthroughs in research. I am confident that scientists at A*STAR will continue to step across the boundaries of traditional research disciplines and produce exciting and groundbreaking work as Singapore strives towards being Asia's Innovation Capital."

###

Notes to the Editor:

Research publication: The research findings described in the press release can be found in the 2011 advance online issue of Stem Cells under the title "Conversion of Sox17 into a Pluripotency Reprogramming Factor by Re-engineering its Association with Oct4 on DNA".

Authors: Ralf Jauch1#, Irene Aksoy2#, Andrew Paul Hutchins2,3#, Calista Keow Leng Ng1,4, Xian Feng Tian2, Jiaxuan Chen2, Paaventhan Palasingam1, Paul Robson2,5, Lawrence W. Stanton2,5* and Prasanna R Kolatkar1,5*

1 Laboratory for Structural Biochemistry, Genome Institute of Singapore
60 Biopolis St, Singapore 138672

2 Stem Cell and Developmental Biology, Genome Institute of Singapore
60 Biopolis St, Singapore 138672

3 Current address: Immunology Frontier Research Centre, Osaka University, 3-1
Yamadaoka, Suita, Osaka, Japan, 565-0871

4 School of Biological Sciences, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798

5 Department of Biological Sciences, National University of Singapore, 117543

# Equal contribution
*Corresponding authors : Lawrence W. Stanton, Ph.D., and Prasanna R. Kolatkar, Ph.D., Genome Institute of Singapore,
60 Biopolis Street #02-01, 138672 Singapore. Phone: +65 6808 8006 ; Fax: 6808 8291; e-mail: stantonl@gis.astar.edu.sg or kolatkarp@gis.a-star.edu.sg

About the Genome Institute of Singapore

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine. The key research areas at the GIS include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

For more information about GIS, please visit www.gis.a-star.edu.sg

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and six consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity.

A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, hospitals, research centres, and with other local and international partners.

For more information about A*STAR, please visit www.a-star.edu.sg.

For more information, please contact:

Winnie Serah Lim (Ms)
Genome Institute of Singapore
Corporate Communications
Tel: (65) 6808 8013
Email: limcp2@gis.a-star.edu.sg

Prudence Yeo (Ms)
Corporate Communications
Genome Institute of Singapore
Corporate Communications
Tel: (65) 6808 8010
Email: yeojp@gis.a-star.edu.sg

END

ELSE PRESS RELEASES FROM THIS DATE:

Blood test confirmed to be 'powerful predictor' following largest analysis to date

2011-05-19

Washington, DC – Researchers at Georgetown Lombardi Comprehensive Cancer Center say the number of circulating tumor cells (CTCs) in the blood is a "powerful predictor" to help physicians more reliably assess treatment benefit for patients with metastatic breast cancer. The findings from a large analysis using pooled data from international cancer centers will be presented during a poster session on Monday, June 6th, at the 2011 annual meeting of the American Society of Clinical Oncology in Chicago. "The current standard of care for monitoring patients with metastatic ...

New treatment regimen shows clinical benefit in advanced colon cancer

2011-05-19

Washington, D.C. -- A new treatment regimen for patients with metastatic colon cancer appears to offer clinical benefit even when used after multiple other treatments have failed, say research physicians at Georgetown Lombardi Comprehensive Cancer Center, a part of Georgetown University Medical Center. The research team found that combining a PARP inhibitor with chemotherapy (temozolomide) offers significant benefit in patients who had no further treatment options. However, the study is small, and does not include a comparison arm, so further investigation is needed, ...

Heart drugs ineffective in treating pulmonary arterial hypertension

2011-05-19

ATS 2011, DENVER – Despite their beneficial effects in treating heart disease, neither aspirin nor simvastatin appear to offer benefit to patients suffering from pulmonary artery hypertension (PAH), according to a National Institutes of Health (NIH)-funded study conducted at four U.S. medical centers. This was the first NIH-funded randomized clinical trial (RCT) in PAH. The results of the study will be presented at the ATS 2011 International Conference in Denver. PAH is a progressive, incurable disease characterized by increased blood pressure in the arteries of the ...

Maternal smoking causes changes in fetal DNA

2011-05-19

ATS 2011, DENVER - Children whose mothers or grandmothers smoked during pregnancy are at increased risk of asthma in childhood, but the underlying causes of this are not well understood. Now a new study indicates changes in a process called DNA methylation that occurs before birth may be a root cause. The study will be presented at the ATS 2011 International Conference. DNA methylation is a process that can alter a gene's usual function. These altered genes can be passed along from parent to child. In this case, researchers observed DNA methylation-related changes ...

Standing up to fight

2011-05-19

SALT LAKE CITY, May 18, 2011 – A University of Utah study shows that men hit harder when they stand on two legs than when they are on all fours, and when hitting downward rather than upward, giving tall, upright males a fighting advantage. This may help explain why our ape-like human ancestors began walking upright and why women tend to prefer tall men. "The results of this study are consistent with the hypothesis that our ancestors adopted bipedal posture so that males would be better at beating and killing each other when competing for females," says David Carrier, ...

UCSF team discovers key to fighting drug-resistant leukemia

2011-05-19

Doctors who treat children with the most common form of childhood cancer – acute lymphoblastic leukemia – are often baffled at how sometimes the cancer cells survive their best efforts and the most powerful modern cancer drugs. Now a team of scientists led by researchers at the University of California, San Francisco have uncovered the basis for this drug resistance: BCL6, a protein that leukemia cells use to stay alive. Targeting this protein may be the key to fighting drug-resistant leukemia, a discovery that may make cancer drugs more powerful and help doctors formulate ...

Auto Recyclers Seek EPA Retraction of Stormwater Permit Guidance Memorandum

2011-05-19

Today, the Automotive Recyclers Association (ARA) urged the Environmental Protection Agency (EPA) to retract its November, 2010 Guidance Memorandum that encourages state permitting authorities to measure industrial stormwater discharges through numeric effluent limits rather than use the traditional and effective best management practices (BMP) approach. "This Memorandum goes well beyond simply updating a policy as EPA suggests," says ARA's CEO Michael E. Wilson. "Rather, it appears to represent a major shift in how best to measure stormwater discharges - ...

The Earth's core is melting ... and freezing

2011-05-19

The inner core of the Earth is simultaneously melting and freezing due to circulation of heat in the overlying rocky mantle, according to new research from the University of Leeds, UC San Diego and the Indian Institute of Technology. The findings, published tomorrow in Nature, could help us understand how the inner core formed and how the outer core acts as a 'geodynamo', which generates the planet's magnetic field. "The origins of Earth's magnetic field remain a mystery to scientists," said study co-author Dr Jon Mound from the University of Leeds. "We can't go and ...

HeliScopeCAGE: A new gene expression analysis technique on a single molecule sequencer

2011-05-19

A new gene expression technique adapted for single molecule sequencing has enabled researchers at the RIKEN Omics Science Center (OSC) to accurately and quantitatively measure gene expression levels using only 100 nanograms of total RNA. The technique, which pairs RIKEN's Cap Analysis of Gene Expression (CAGE) protocol with the Helicos® Genetic Analysis System developed by Helicos BioSciences Corporation, opens the door to the detailed analysis of gene expression networks and rare cell populations. In recent years, next-generation DNA sequencers have produced an increasingly ...

Breaking News! 2011 Urologist Report Reveals "Traction Beats Surgery for Permanent Lengthening of the Male Sex Organ"

2011-05-19

Penile enlargement is one of the most controversial topics today. Many physicians claim that there is no medical proof that the non-surgical methods for increasing the penile size actually work. In addition to that, there are many people online abusing this topic, which is one of the main reasons why everyone is so skeptic about it. With the growing popularity of the penile extenders, one of the most reputable medical journals BJUI (British Journal of Urology International), which is issued as the official journal of the British Association of Urological Surgeons, have ...

LAST 30 PRESS RELEASES:

Linearizing tactile sensing: A soft 3D lattice sensor for accurate human-machine interactions

Nearly half of Australian adults experienced childhood trauma, increasing mental illness risk by 50 percent

HKUMed finds depression doubles mortality rates and increases suicide risk 10-fold; timely treatment can reduce risk by up to 30%

ECMWF and European Partners win prestigious HPCwire Award for "Best Use Of AI Methods for Augmenting HPC Applications” – for AI innovation in weather and climate