Studentships starting October 2012
Application deadline 13 January 2012
Interviews to be held 30-31 January 2012

Stem Cell Biology

Stem cells are defined by the dual capacity to self-renew and to differentiate. These properties sustain homeostatic cell turnover in adult tissues and enable repair and regeneration throughout the lifetime of the organism. In contrast, pluripotent stem cells are generated in the laboratory from early embryos or by molecular reprogramming. They have the capacity to make any somatic cell type, including tissue stem cells.

Stem cell biology aims to identify and characterise which cells are true stem cells, and to elucidate the physiological, cellular and molecular mechanisms that govern self-renewal, fate specification and differentiation. This research should provide new foundations for biomedical discovery, biotechnological and biopharmaceutical exploitation, and clinical applications in regenerative medicine.

Cambridge Stem Cell Community

The University of Cambridge is exceptional in the depth and diversity of its research in Stem Cell Biology, and has a dynamic and interactive research community that is ranked amongst the foremost in the world. By bringing together members of both the Schools of Biology and Medicine, this four year PhD programme will enable you to take advantage of the strength and breadth of stem cell research available in Cambridge. Choose from over 30 participating host laboratories using a range of experimental approaches and organisms.

Programme Outline

During the first year students will:
• perform laboratory rotations in three different participating groups working on both basic and translational stem cell biology;
• study fundamental aspects of Stem Cell Biology through a series of teaching modules led by leaders in the field;
• learn a variety of techniques, such as advanced imaging, flow cytometry, and management of complex data sets.

Students are expected to choose a laboratory for their thesis research by June 2013, and will then write a research proposal which will be assessed for the MRes Degree in Stem Cell Biology. Students will then normally commence a three year PhD.
Visit http://www.stemcells.cam.ac.uk/careers-study/studentships/ for full details.

(1 votes)

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This book review originally appeared in Development. Wendy Bickmore reviews “The Nucleus” (Edited by Tom Misteli and David L. Spector).

Book info:
The Nucleus Edited by Tom Misteli, David L. Spector Cold Spring Harbor Laboratory Press (2011) 517 pages ISBN 978-0-879698-94-2 $135 (hardback)

Why should a developmental biologist be interested in a book about the nucleus? Almost 80 years ago, Conrad Waddington put forward ideas about how gene products could regulate development. In modern parlance, much of development is the result of the differential use of the same genome in different cell types and at different developmental stages within the same organism. This originates in the nucleus, where the processes that act upon the genome – transcription, replication, repair – occur. In developmental biology papers it is not uncommon to find a final summary figure in which a signaling pathway ends up pointing into an oval-shaped nucleus, devoid of any structure or organization, save for a linear depiction of a target gene locus. However, the nucleus is not a homogenous space and neither is the genome in its natural nuclear environment arranged in a linear fashion.

The contributions in this book, from international leaders in the field of nuclear organization and function, are based upon the premise that we cannot really understand how genomes function without an appreciation and understanding of their natural cellular environment – the nucleus.

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(6 votes)

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Book Info:  The Cell: A Very Short Introduction by Terence Allen and Graham Cowling. Oct 2011. 152 pages. ISBN: 9780199578757 (Paperback) Price: $11.95 /£7.99

Ever since Anton van Leeuwenhoek first peered at a living cell in 1674, scientists have been driven to learn everything they can about these tiny units of life and as a result have been developing ever more advanced tools to observe, describe and manipulate them. In the book “The Cell”, a new addition to the Oxford University Press Very Short Introductions series, Terence Allen and Graham Cowling undertook an enormous task of distilling several hundred years of cell biology research into 145 pages including 8 chapters, a further reading section, an index, a glossary and 17 illustrations.  The result is that an enormous amount of information is presented in pithy vignettes covering everything from the inner workings of the cell up to the complex interactions of cells within multicellular organisms, as well as cellular disease and directions for future research.

Chapter 1 introduces cells as highly efficient factories capable of maintaining and replicating themselves as well as interacting with and responding to their surroundings.  It includes a description of the unifying concepts common to all cells such as cellular components, subcellular organization, and life processes as well as the diversity of cells, their specialized functions and adaptations to various environments. Frequently, generalizations about particular types of cells (prokaryotic or eukaryotic, plant or animal) are intertwined with very specific information such as size of various cytoskeletal filaments.

The following two chapters introduce the subcellular components and describe how these work together to orchestrate the cell’s day-to-day function.  The nucleus and organization of the genome as well as a brief description of gene structure are described in their own chapter.

Chapter 4 and 5 discuss various processes of a cell’s life such as division, DNA replication, movement and apoptosis (programmed cell death).  Additionally there is a description of various types of specialized, differentiated cells found in multicellular organisms.  The focus is primarily on animal cells, however plant cells and bacteria living in extreme environments are briefly mentioned.

Chapter 6 focuses on stem cells in living organisms, both embryonic and adult.  Included is the definition of a stem cell, a brief history of the field and a discussion of cancer stem cells.

Chapter 7 discusses cell-based therapies from early attempts to modern applications such as blood transfusions as well as the possibilities that embryonic stem (ES) cell research offers.  The ethical debate regarding stem cells is mentioned and there is a discussion of possible applications of stem cells in the treatment of several cellular diseases such as muscular dystrophy and diabetes.

Chapter 8 focuses on the future of cell research.  It introduces fields of systems biology, synthetic biology, regenerative medicine and includes a speculative discussion about the possibility of reversing aging in the future.

A small criticism that I have is that despite the short length of the book some errors slipped through the editing process. Most notable is that the description of gene structure incorrectly names the coding sequences “introns” and the non-coding “exons”.  Although the correct definition is provided in the glossary this error might confuse a novice student of biology, especially because these terms are counterintuitive.

The illustrations, which, except for a few diagrams, are all black and white electron microscope (EM) images showing cell surfaces and subcellular structures.  The images are relevant and interesting, but for someone not used to looking at pictures of cells or EM images these might not provide as much information or generate as much interest as the authors intended.

Overall “The Cell” makes for informative and entertaining reading. The concentrated and comprehensive information provided are a perfect refresher to any biologist who wants to be reminded of the basics of cell biology or a novice biology enthusiast who wants to delve into the microscopic world of cells without the intimidation of a textbook. Although the focus is mostly on eukaryotic animal cells, those aspects that distinguish prokaryotes and plant cells are frequently pointed out. The historical anecdotes that accompany descriptions of various discoveries as well as the thought-provoking discussions about the future prospects for the biomedical applications of cell research made this book particularly enjoyable for me. For those readers who find themselves wanting to learn more the authors provide a list of resources for further reading, both books and online resources.

(5 votes)

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Many of you may have a few days off from work at the moment. If you want to catch up on what you missed on the Node this month, read on:

BenchFly bingo game

Benchfly, a site with free video protocols and other resources for researchers, has created “Group Meeting Bingo”. The site generates bingo cards with the particular phrases common to various fields of research. They have cards for biochemistry, cell biology, and various other fields, but no developmental biology…yet!

So, let’s make a developmental biology bingo game!

Add suggestions for words to include to the post. We already have quite a few, but I’m sure you’ll find something that hasn’t been mentioned yet. You still have this weekend to add words.

Rejuvenating old cells

With the new year approaching, you may have been pondering the passage of time lately. Another year gone, another year older. But there’s hope still! Sasha wrote about a recent paper that shows that your cells are never too old for pluripotency!

“(…) Researchers began to wonder whether cellular aging was a barrier to iPS cell conversion. In a recent paper published the November issue of Genes in Development, entitled “Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state,” Lapasset and colleagues from the Institute of Functional Genomics in France report that they have overcome this barrier and generated iPS cells from human donors as old as 101 years.”

Book reviews

Continuing from last month, we’ve republished more book reviews from Development. Click on a cover to read the review.

Also on the Node:
– Dates and deadlines, including an extended early registration deadline for the LASDB meeting
-“Pigs that Fly” – Jonathan’s third rotation lab for the Wellcome Trust PhD programme.
– For more, see the full December archive.

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This book review originally appeared in Development. Melissa Mann reviews “Epigenetics: Linking Genotype and Phenotype in Development and Evolution” (Edited by Benedikt Hallgrímsson and Brian K. Hall).

Book info:
Epigenetics: Linking Genotype and Phenotype in Development and Evolution Edited by Benedikt Hallgrímsson, Brian K. Hall University of California Press (2011) 472 pages ISBN 978-0520267091 (hardback), 978-0520948822 (eBook) £59/$68 (hardback), $85 (eBook)

Ask ten scientists their definition of epigenetics and you may get ten answers. In its simplest form, epigenetics can be defined as above (epi) the level of genes (genetics), and in the book entitled Epigenetics: Linking Genotype and Phenotype in Development and Evolution, the editors, Benedikt Hallgrímsson and Brian K. Hall, have assembled 23 chapters that collectively embody epigenetics as described by this broad definition. Although the book is organized into four parts, it can be distilled into three themes that each discusses a more detailed interpretation of the field: molecular epigenetics, classical epigenetics/epigenetic interactions, and epigenetic interactions and evolution.

In its modern molecular reiteration, epigenetics is defined as a change in gene activity without a change in DNA sequence. Most molecular definitions of epigenetics also include the idea of heritability, or memory of gene activity, through cell division. Here, epigenetic modifications modulate gene expression through DNA methylation, histone modifications, changes in chromatin structure, and effects of non-coding RNAs. This book includes five chapters on molecular epigenetics, covering various organisms and topics from asexual organisms in the study of epigenetic variation to epigenetics and human disease. One chapter highlights neural development in which cell-fate switches are intimately linked with epigenetic changes. For example, transition from a neural stem cell to a progenitor cell involves a switch in co-factor associations. In response to Notch effector molecules, the HES1 repressor complex is transformed into a HES1 activator complex, thereby inducing a progenitor cell fate. A different mechanism may be utilized in neuronal fate specification in the neocortex. Changes in DNA looping and nuclear matrix binding may specify an upper layer neocortical fate. This chapter describes the current understanding of various epigenetic mechanisms involved in neural cell fate decisions.

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(3 votes)

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The Cell: An Image Library™ offers you a little fun this week. Please enjoy our quiz, Celestial or Cellular?
Take a look at the images and see if you can tell whether they are of cellular or celestial origin.
Take your best shot, and enter your answers at http://asterisk.apod.com/viewtopic.php?f=29&t=26228. Visit again each day this week for a new quiz and the correct answers to the previous day’s quiz.
Enjoy, and please share this with your friends.
Visit The Cell: An Image Library and learn how to submit your images.
Reuse of quiz images may be subject to licensing restrictions, which will be revealed with the identity of the image on the day following the quiz.

(2 votes)

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Many tissues and organs contain self-renewing stem cell populations that are crucial for their maintenance. Synthesizing the relative effects of anatomical constraints, cell proliferation dynamics and cell fate specification on the overall stem cell population dynamics is challenging, and so we reasoned that dynamic computational models that have the potential to systematically manipulate different influences might facilitate an understanding of experimental studies on self-renewing cell populations.

In our study published in Development [1] we have built a computational model of germline development in C. elegans. In this model, germ cells move, divide, respond to signals, progress through mitosis and meiosis, and differentiate according to a developmental program specified for a “cell”. This developmental program incorporates cellular decision-making that influences germ cell behavior, as defined by a subset of cell components and their dynamic interactions. Simulations driven by the model recapitulate C. elegans germline development and the effects of various genetic manipulations, as shown in supplementary movies, also available at [2].

Our analyses of model simulations and laboratory studies suggest that: (1) when the ligand interaction occurs over a short distance (that is, reaching only the distal-most germ cells), small differences in this distance destabilize the system and introduce unexpected variability; (2) inherent differences between progenitor cell types need not necessarily be invoked to explain complex differentiation dynamics upon reduction of receptor activity; (3) population dynamics and anatomical constraints influence niche residence; and (4) the germ cell proliferation rate during larval stages influences the differentiation pattern in the adult.

The computational modeling in this project has been carried out in the computational science laboratory at Microsoft Research in Cambridge, in close collaboration with the Hubbard lab. We are applying and developing modeling methods that were originally introduced for building and understanding engineering and software systems. Since biological systems are far more complex and robust than man-made engineering systems, a long term goal of this research is to challenge the ways engineering and software systems are currently constructed and understood.

[1] Y. Setty, D. Dalfo, D.Z. Korta, E.J. Albert Hubbard, and H. Kugler, A model of stem cell population dynamics: in-silico analysis and in-vivo validation, in Development, vol. 139, 47-56, 2012.

[2] http://research.microsoft.com/celegans

(3 votes)

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The University of Tsukuba, Japan is offering fully-funded PhD studentships to do research in Japan. They have close ties with many international universities, including the University of Edinburgh. Joint projects between Edinburgh and Tsukuba will be available. The University of Tsukuba, located 1 hour from Tokyo, is one of the top universities in Japan, and does outstanding biological research. All courses and research will be in English.

Please visit this site for further details and for application forms: http://hbp.tsukuba.ac.jp/en/

The deadline is 4th January, 2012, and interviews will be held in Edinburgh on 22nd and 23rd January.

Send informal enquires to both Tilo Kunath (tilo.kunath@ed.ac.uk) and Prof Satoru Takahashi (satoruta@md.tsukuba.ac.jp)

(2 votes)

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It’s been a busy year for EuroStemCell: Europe’s stem cell hub – see www.eurostemcell.org for more information on who we are. We’d like to wish The Node community a happy festive season and a great start to 2012. But before we say goodbye to 2011, we thought you might be interested to know about some of the things we’ve been doing recently…

EuroStemCell goes multilingual

Research updates from EU-funded stem cell projects

Our research updates keep you informed about progress in public-funded European stem cell research. Here’s a recent example from our partner, NeuroStemcell.

Using stem cells to develop new therapies for Parkinson’s and Huntington’s diseases

NeuroStemcell brings stem cell biology and clinical science together to develop and test new approaches to stem-cell-based therapy. We study Parkinson’s (PD) and Huntington’s (HD) diseases, which are degenerative diseases of the brain.

Read more about NeuroStemcell

Italy meets the UK to discuss the future of stem cells in the clinic

Inside the lab

We’ve got two new guest bloggers on our site: Anestis Tsakiridis is sharing his insider’s view of stem cell research in his blogs, Behind the Bench: A series about researchers and their rituals; and we’re delighted to welcome Alzheimer’s researcher Selina Wray, who posted her first blog, A fish out of water, on our site just last week.

Meet the stem cell scientists

We’ve also been busy talking to experts across the stem cell field. Read our interviews with Cedric Blanpain, Yann Barrandon, Christine Mummery, Doug Sipp, Karen English and Nick Barker on the site now and keep your eye out for our chats with Jane Visvader, Connie Eaves and others in the New Year.

Stem cell factsheets

Keep up with Europe’s stem cell news

Sign up to our newsletter to stay in touch with all the latest news from the EuroStemCell project. From February 2012 we’ll be sending out a  monthly newsletter. For more regular updates, you can follow us on Twitter, check out our Facebook page or subscribe to our RSS feeds.  And if you haven’t visited the site for a while, do take a look and get in touch with your feedback and ideas.

(2 votes)

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This book review originally appeared in Development. Neil Singh and Ludovic Vallier review “Human Stem Cell Technology and Biology” (Edited by Gary S. Stein, Maria Borowski, Mai X. Luong, Meng-Jiao Shi, Kelly P. Smith and Priscilla Vasquez).

Book info:
Human Stem Cell Technology and Biology: A Research Guide and Laboratory Manual Edited by Gary S. Stein, Maria Borowski, Mai X. Luong, Meng-Jiao Shi, Kelly P. Smith, Priscilla Vasquez Wiley-Blackwell (2011) 419 pages ISBN 978-0-470-59545-9 £93.50/€112.20 (hardback)

Do we need another book on human stem cell biology? The field is fairly long in the tooth now, thirteen years after Thomson first derived human embryonic stem (ES) cells (Thomson et al., 1998). There are many books that cover the theoretical aspects of the discipline (Oderico et al., 2004) and others that attempt to collate protocols useful to human stem cell biologists (Sullivan et al., 2007). Nevertheless, the new book Human Stem Cell Technology and Biology succeeds in combining both of these characteristics, providing not only a clear account of the scientific discoveries underpinning human stem cell biology, but also a useful range of laboratory protocols. The end product may be less comprehensive than Lanza’s classic text (Lanza et al., 2009), but it is perhaps more manageable and appropriate for a newcomer to the field or for an early career scientist working with human pluripotent cell lines for the first time.

The editors are all based at the Center for Stem Cell Biology & Regenerative Medicine at the University of Massachusetts Medical School. The individual chapters are written predominantly by scientists from institutes on the East coast of the United States, although some contributors are based in Australia, Canada and China. The book is divided broadly into five sections: an introduction; two sections on the culture and characterisation of human pluripotent stem cells; and two sections covering more recent technologies and applications relevant to human ES cells.

In the introduction, the authors have managed to distill over 50 years of stem cell advances in just a few pages of text. Although this may be too short for experienced scientists hoping for a colourful narrative history of each breakthrough, we think it does well to bring even novice readers up to speed with current thinking in stem cell biology, from the bottom up.

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