A*STAR Release: Cells Decoded: Scientists Discover How Cells Build Their Inner Skeletons

SINGAPORE, 1 SEPT 2017 – Scientists at Singapore’s Agency for Science, Technology and Research (A*STAR) have discovered how mammalian cells build their internal skeletons during the earliest stages of life.

The research team, led by Dr Nicolas Plachta at the Institute of Molecular and Cell Biology (IMCB), believe this discovery will form the basis for new methods to monitor normal versus abnormal development of human embryos cultured in vivo, and used for assisted reproduction (IVF) and preimplantation genetic diagnosis (PGD). The team’s findings were published in leading scientific journal Science on 1 September 2017.

Every cell in the body has an internal skeleton made of hundreds of fibres called microtubules. Microtubules grow from a region of the cell known as the centrosome. However, in the early stages of embryonic development, cells lack centrosomes;

therefore it has long been a mystery how cells begin to build their skeletons during the earliest stages of life. The IMCB researchers used laser imaging technologies to study live mouse embryos, which develop extremely similarly to humans during early embryonic stages of life. This led to the discovery of a structure inside the cells from which the microtubules that form the cell’s skeleton begin to emanate. This newly discovered structure called the “microtubule organising centre”, acts as the centrosome of the cell before its formation. Moreover, when the scientists used nanolasers to disrupt this structure in cells, they found this resulted in embryos with disorganised microtubule networks that were unable to develop normally.

Dr Jennifer Zenker, a postdoctoral fellow in Dr Plachta’s lab and first author of the study, said about the discovery: “Our study advances our understanding of how a healthy embryo forms during the pre-implantation stages of development, before the embryo implants into the uterus.”

Dr Nicolas Plachta, Senior Principal Investigator in IMCB and lead author of the study, said: “Our findings open up possibilities for designing new, non-invasive ways to visualise the cytoskeleton of cells in the early human embryo, and monitoring which embryos develop normally for procedures such as IVF and PGD. The discovery could also help shed light on new strategies to treat diseases linked to abnormalities in the cell cytoskeleton, such as infertility and neurodegeneration.”

Moving forward, the IMCB team plans to study how the “microtubule organising centre” in the early mammalian embryo controls embryonic development, cell differentiation, and intracellular transport.

Encl: ANNEX A – NOTES FOR EDITOR

ANNEX B – BIOGRAPHIES OF KEY SCIENTISTS

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About A*STAR’s Institute of Molecular and Cell Biology (IMCB)

The Institute of Molecular and Cell Biology (IMCB) was launched on 23 January 1985, with its official opening ceremony held on 2 October 1987 at the National University of Singapore (NUS). It subsequently became an autonomous research institute (RI) of A*STAR, moving to Biopolis in 2004. IMCB’s vision is to be a premier cell and molecular biology institute which addresses the mechanistic basis of human diseases and its mission is to conduct cutting-edge discovery research in disease pathways; to groom early career researchers to be future leaders in research; and to collaborate with medical and industry communities for research impact. IMCB plays an important role training and recruiting scientific talents, and has contributed to the development of other research entities in Singapore. Its success in fostering a biomedical research culture in Singapore has catalysed Singapore’s transformation into an international hub for biomedical research, development and innovation.

Funded primarily by the Biomedical Research Council (BMRC) of A*STAR, IMCB’s Discovery research comprises 5 major programmes: Cancer Cell Signalling, Multi-Modal Molecular (M3) Biology, Epigenetics and Diseases, iPS cell and Regenerative Medicine, and Technology and Translation. IMCB’s technologies and platforms focus on Genome-wide RNAi, Humanized Mouse Models, Proteomics and Protein Engineering, Gene Therapy and Gene Editing, and Molecular Histopathology.

IMCB strives to maintain the scientific excellence of PI-driven research and at the same time aims to promote collaborative team-based projects of medical and industrial relevance.

For more information about IMCB, visit www.imcb.a-star.edu.sg.

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

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.

As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.

We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and Research Institutes, the wider research community and industry. A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities primarily located in Biopolis and Fusionopolis.

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

ANNEX A

NOTES FOR EDITOR:

The research findings described in this scientific advisory can be found in the 1st September 2017 issue of the scientific journal Science, under the title, “A Microtubule Organizing Center Directing Intracellular Transport in the Early Mouse Embryo” by J. Zenker,1 M.D. White,1 R.M. Templin,2 R.G. Parton,2 O. Thorn-Seshold,3 S. Bissiere,1 N. Plachta1,4*

1Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore

2Institute for Molecular Biosciences and Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, Queensland, Australia

3Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-University Munich, Munich, Germany

4Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

*Correspondence should be addressed to Nicolas Plachta (plachtan@imcb.a-star.edu.sg) After lifting of the embargo, full text of the article can be accessed from: http://science.sciencemag.org/cgi/doi/10.1126/science.aam9335

ANNEX B

BIOGRAPHIES OF KEY SCIENTISTS:

Dr Nicolas PLACHTA

Dr Plachta studied biology at the University of Buenos Aires (Argentina) and University of Tel-Aviv (Israel). He did his PhD with Yves-Alain Barde at the Biozentrum (University of Basel, Switzerland) and postdoc in biological imaging with Scott Fraser at Caltech (US), supported by fellowships from Swiss National Foundation, EMBO and CIRM. Dr Plachta was appointed Group Leader at EMBL Australia in 2011 and joined A*STAR in 2015 as Senior PI under the A*STAR Investigatorship Programme, a platform to support and promote early independence and career development of future world leaders in scientific research. His accomplishments and potential in the area of molecular biology have been recognised by several prominent research organisations around the world, including fellowships from the Swiss National Science Foundation, EMBO, California Institute of Regenerative Medicine, Viertel Foundation, and Australian NHMRC and ARC.

In 2015, Dr Plachta became one of five scientists outside of Europe to be selected for the EMBO Young Investigator Programme since its launch in 2000. In 2016, he was awarded the American Society for Cell Biology (ASCB) Gibsco Emerging Leader Prize, which honours emerging leaders in science. In 2017, he was recognised as a Howard Hughes Medical Institute (HHMI) International Scholar.

Dr Plachta’s main research interest lies in understanding how mammalian life begins by studying living embryos in real time using cutting-edge cell imaging techniques. Through in-depth examination on the formation and development of mouse embryos, Dr Plachta’s research enables the identification of biological pathways and signatures linked to fertility hence pave the way to the development of novel therapeutic solutions to human infertility.

Dr Jennifer ZENKER

Dr Jennifer Zenker has been recognised for her ongoing research in single-cell imaging of the living pre-implantation mouse embryo. She is currently a Postdoctoral Fellow in the lab of Dr Nicolas Plachta at IMCB, A*STAR. Located within the Discovery Research Division of IMCB, the Plachta lab focuses primarily on imaging live mouse embryos in real-time using advanced imaging technologies.

Dr Zenker studied Biology at the University of Stuttgart-Hohenheim (Germany), and obtained her Ph.D. in Neurobiology from the University of Lausanne, Switzerland, in 2012. From 2012-2014, she was a senior researcher at the Department of Medical Genetics at the University of Lausanne. Since 2014, she has worked with Dr Plachta as a postdoctoral fellow, both at the European Molecular Biology Laboratories (EMBL, Australia, 2014 to 2015), and at IMCB, A*STAR (Singapore, 2015 to present).

Dr Zenker has been the recipient of numerous fellowships and awards, including the Deutsche Forschungsgemeinschaft (DFG) Postdoctoral Fellowship in 2013. The DFG is a key German research funding organization and the largest of its kind in Europe. Dr Zenker’s work has led to publications in journals such as PLoS Genetics (2015), Glia (2014), Human Molecular Genetics (2013, 2014), Journal of Neuroscience (2012), Trends in Neuroscience (2012), Brain (2010), and PNAS (2009). For her ongoing and innovative contributions to the field of molecular and cell biology, Dr Jennifer Zenker was the recipient of the 2015 Human Frontier Science Program (HFSP) Long-Term Postdoctoral Fellowship. Page

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