Stem cell encyclopedia leads to new stem cells

Embargoed, National Stem Cell Foundation of Australia

An online encyclopedia created by Christine Wells has led to the discovery of a new kind of stem cell. And that’s just the beginning. Christine’s small Brisbane team has created a resource that the global stem cell research community is using to rapidly share knowledge and fast track stem cell discoveries.

In recognition of her leadership in stem cell research, Associate Professor Christine Wells of the University of Queensland and the University of Glasgow has received one of two $50,000 Metcalf Prizes from the National Stem Cell Foundation of Australia.

Stem cell science is a growing field of research with huge potential to save lives.

“The stem cell field is growing so fast, it can be hard for researchers to keep abreast of the know-how and data that’s accumulating outside their particular special interest,” says Christine. “I’m working to address that need.”

Christine leads the Stemformatics initiative—an online encyclopedia of detailed scientific information on how our thousands of different genes shape us—putting vital data at the fingertips of stem cell researchers and their cross-disciplinary collaborators.

Christine and her encyclopedia helped a global team of 50 scientists from four countries, led by Canadian Andras Nagy, to access, share and integrate an enormous amount of data. This enabled the discovery of F-class stem cells, a whole new class of ‘pluripotent’ stem cell—cells that can give rise to any type of cell—and only the second type that can be grown in the lab from adult tissues.

Christine says the big questions being asked in biomedical science often need many minds to address them.

“What’s really exciting is that we’ve shown with stem cell science how making good quality data available, easy to use and shareable can bring experts together, fast-track research and lead to major discoveries.”

Christine will use her Metcalf Prize to further grow Stemformatics as a powerful resource for the worldwide stem cell research community.

This will allow researchers to interrogate their own data more deeply, compare it with the data of other researchers, gain new insights and perhaps even discover other classes of stem cells with therapeutic potential. It will also help identify knowledge gaps.

Christine is a Group Leader at the Australian Institute for Bioengineering and Nanotechnology at the University of Queensland, Reader in Innate Genomics at the University of Glasgow and Director of the Stemformatics program for Stem Cells Australia.

The award is named for Australia’s pioneering stem cell researcher, the late Professor Donald Metcalf, AC, an internationally renowned expert on blood cell formation, who died late last year.

“We’ve created the Metcalf Prizes to support the rising stars of Australian stem cell science,” says Dr Graeme Blackman, OAM, the Chairman of the Foundation.

“Christine is a unique leader and passionate about collaboration. We’re particularly excited by the knowledge that supporting her work will also support the research of the wider stem cell community.”

Event Thursday 14 May in Brisbane: Christine Wells will be part of a panel of internationally recognised stem cell research leaders, including Alan Trounson and Martin Pera, for a special public forum ‘Translating stem cell research into real health and economic benefits’, moderated by ABC Radio National’s Norman Swan.

Details: http://www.alumni.uq.edu.au/gls-stem-cell

Profile

If scientists are a modern equivalent of pioneering explorers, charting unfamiliar coastlines and revealing new countries, then Christine Wells is part explorer and part master map-maker.

“Imagine asking two people—one who has only lived in Toorak and another who has only lived in Frankston—what Melbourne is like. You might get two very different answers. A similar thing can happen in stem cell science,” explains Christine.

“Stem cell science is moving rapidly. Research is often highly specialised, but areas outside your own expertise can be opaque. I work on what we call ‘atlas’ projects that effectively map and make available detailed information about how different genes are expressed as stem cells divide and specialise.”

Christine and her Stemformatics team collate high quality data from around the world and make it easy for the generalist scientist to use.

“You can look up your favourite genes or favourite types of cells and pull out a huge volume of data to further explore how they work.”

This allows multiple minds from different disciplines to interrogate a veritable goldmine of information, building ‘rules’ or benchmarks for cell behaviour, spotting trends and sometimes unearthing major discoveries.

“It’s a space where statisticians, bioinformaticians—our field’s computer scientists—and stem cell biologists can interact as equals and work together for mutually beneficial outcomes. The stem cell biologists might discover a new stem cell, but the statisticians might develop and refine a new statistical tool.”

Open for discovery; open for scrutiny

The discovery of F-class stem cells—so named because they cluster in ‘fuzzy-looking’ colonies—was an unexpected but welcome surprise, borne of a major international collaborative effort to painstakingly document the molecular events that happen when adult cells are ‘reprogrammed’ or converted into stem cells.

Dubbed ‘Project Grandiose’, it was led by Canadian Andras Nagy. The team shared data and analyses via the Stemformatics platform. The project stumbled upon F-class stem cells along the way.

The research was published in five Nature and Nature Communications journal papers. Christine was a coauthor for four of these papers.

2014 was a year bookended by two different announcements of new adult stem cells.

The December announcement of Project Grandiose’s reprogramming roadmap and the new F-class stem cells—produced with a variation of the technique developed by Nobel prize winner Shinya Yamanaka—capped off a dramatic year for stem cell science.

In January, two Nature papers had announced the discovery of ‘STAP’ stem cells, purportedly made using an acid bath to coax cells back to a stem cell like state. But this research turned out to be fraudulent; a tragic saga that damaged reputations, resulted in a suicide and exposed systematic problems with research transparency and disclosure.

The F-class stem cell discovery was announced to a research community still dealing with the shockwaves from the STAP controversy. Project Grandiose was markedly different, and Stemformatics was at the heart of this difference.

“All of the methods and all of the data are freely and publicly available, not just to the Nature paper reviewers, but to everyone,” says Christine.

“This gives the research community both confidence in findings and the inspiration and means to put these methods and data to use to make their own discoveries.”

An international career

Christine is a recognised pioneer of genomics—the study of the structure and function of an organism’s genome—and its role in immunity and stem cell biology. She discovered the function of several genes involved in the fight against infection, and that regulate inflammation.

Collaboration is at the heart of Christine’s research philosophy. In addition to her membership of the Project Grandiose consortium, Christine has an ongoing and senior role in the international genome consortium Functional Annotation of the Mammalian genome (FANTOM), with the RIKEN institute in Japan. She contributes findings from her research group’s work into the networks of genes that influence stem cell function and immune activation. Working closely with AIBN Associate Professor Ernst Wolvetang, her group also provides FANTOM with a set of high-quality neural (brain) stem cell libraries.

In 2011, Christine established Stemformatics.org – a collaborative hub for Australian and international stem cell researchers that enables investigations into gene signatures that correlate with stem cell function.

Christine holds a joint appointment as reader at the University of Glasgow’s Institute of Infection, Immunity and Inflammation. She divides her time between Australia and Scotland.

Qualifications

2004     Doctor of Philosophy, The University of Queensland

1998     Bachelor of Science (Honours), The University of New England

Career Highlights, Awards, Fellowships, Grants

2012     Queensland Government Smart Futures mid-career Fellowship award 2012-2014

2009     Griffuth University award for early career research excellence

2008     NHMRC Career Development Award 2008-2011

2007     ASMR Queensland Premier Award for health and medical research

2004     University of Queensland Dean’s commendation award for outstanding PhD thesis

Top Five Publications

The FANTOM Consortium, Gough, J., Frith, M. C., Ravasi, T., Wells, C., Forrest, A. R. R., Davis, M. J., Aturaliya, R. N., Bailey, T. L., Crowe, M. L., Faulkner, G., Pang, K. C., Teasdale, R. D., Grimmond, S. M., Mattick, J. S., Hume, D. A. and RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Core Team) (2005) The transcriptional landscape of the mammalian genome. Science, 309 5740: 1559-1563. doi:10.1126/science.1112014 (Impact factor = 31, Citations = 1,900+)

Mar, Jessica C., Matigian, Nicholas A., Mackay-Sim, Alan, Mellick, George D., Sue, Carolyn M., Silburn, Peter A., McGrath, John J., Quackenbush, John and Wells, Christine A. (2011) Variance of gene expression identifies altered network constraints in neurological disease. PLoS Genetics, 7 8: . doi:10.1371/journal.pgen.1002207 (Impact factor = 8, Citations = 33)

Wells, Christine A., Mosbergen, Rowland, Korn, Othmar, Choi, Jarny, Seidenman, Nick, Matigian, Nicholas A., Vitale, Alejandra M. and Shepherd, Jill (2013) Stemformatics: visualisation and sharing of stem cell gene expression. Stem Cell Research, 10 3: 387-395. doi:10.1016/j.scr.2012.12.003 (Impact factor = 4, Citations 9)

Tonge, Peter D., Corso, Andrew J., Monetti, Claudio, Hussein, Samer M. I., Puri, Mira C., Michael, Iacovos P., Li, Mira, Lee, Dong-Sung, Mar, Jessica C., Cloonan, Nicole, Wood, David L., Gauthier, Maely E., Korn, Othmar, Clancy, Jennifer L., Preiss, Thomas, Grimmond, Sean M., Shin, Jong-Yeon, Seo, Jeong-Sun, Wells, Christine A., Rogers, Ian M. and Nagy, Andras (2014) Divergent reprogramming routes lead to alternative stem-cell states. Nature, 516 7530: 192-197. doi:10.1038/nature14047 (Impact factor = 42, Citations = 11)

Arner, Erik, Beckhouse, Anthony, Briggs, James, Ovchinnikov, Dmitry, Wolvetang, Ernst, Wells, Christine and FANTOM Consortium (2015) Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science, 347 6225: 1010-1014. doi:10.1126/science.1259418 (Impact factor = 31, Citations = 3)