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ISSCR Annual Meeting – Day 4

Posted by , on 18 June 2013

Final day at the ISSCR. No posters. No concurrent sessions.  Just pure plenary all day. And indeed, the eclectic mix of talks provided a fitting end to 4 days of diverse science.

Ian Chambers kicked things off with an excellent talk describing the surprising recent finding by his laboratory that reduced levels of Oct4 actually improves self-renewal of mouse ES cells and reduces heterogeneity. Elena Cattaneo presented some beautiful stainings of early neural development in human fetuses, work that will surely interest many in the field, while Oliver Brustle gave a good overview of his laboratories work in modelling neural disease using neural stem cells derived from pluripotent stem cells. Benoit Bruneau described his labs impressive efforts to characterise the epigenome of cells at various stages during in vitro cardiac differentiation while Mitinori Saitou provided fascinating insights into the transcription factor control of primoridal germ cell specification. The morning talks were noteworthy not only for their high quality but also the diversity of experimental approaches used; including an assortment of pluripotent stem cell manipulations, reprogramming strategies, in vitro differentiation, -omics, and human in vivo studies.

The afternoon session talks were equally strong. Ken Zaret introduced characteristically meticulous work looking at pioneer transcription factors and the manipulation of chromatin states during both cellular differentiation and reprogramming. Kristin Baldwin presented her recent attempts to characterise the somatic mutational spectra using the formidable combination of somatic cell nuclear transfer (using terminally differentiated neurons) followed by ES cell derivation and whole genome sequencing! The theme of nuclear transfer then continued as one of the most eagerly awaited speakers – Shoukhrat Mitalipov – took to the stage. The recent publication of his derivation of cloned human ES cells created a major stir in the build up to the conference and many were eager to hear the full story of this major feat. They weren’t disappointed and were also treated to his thoughts on the applicability of this technique in the treatment of mitochondrial diseases. Next, Shinya Yamanka returned to the platform to present Marius Wernig with the ISSCR Outstanding Young Investigator Award. Wernig was then given the opportunity to present the work that merited this accolade, namely his groundbreaking studies on trans-differentiation. As well as giving the background to these landmark findings he presented more recent data in which he has taken an –omics approach to try and better characterise the process – including slavishly mapping the binding pattern of the ‘reprogramming’ factors in different cellular contexts. His talk provided an indication that not all his chosen transcription factors function in the same way during the transdifferentiation process, and he presented evidence of pioneer factor activity – an interesting link to Ken Zaret’s talk. Next, the topic shifted to regenerative medicine and included fascinating talks from Hans Snoeck, Graziella Pellegrini and Timothy Bertram. The later two presentations featured data generated following cell transplantation into patients – a goal of many in the field and an exciting way to finish the conference. However, there was just enough time for Eric Lander to provide an intriguing insight into his adventures unlocking the secrets of the human genome – admitting in the process that everything he taught his undergraduate students about the human genome in 2001 has now been proven wrong! I wonder what he taught this year that will suffer the same fate…?!

With a goodbye from Shinya Yamanaka, in his own inimitable style, the 2013 ISSCR came to an end. Although one final surprise came in the lobby where we were met by not only a free bar, but a free bar with some decent beers behind it too! Next year rolls on to Vancouver – although this blogger may well be hanging up his keyboard well before then!

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Day 1 at the ISDB- Sun, science and origami

Posted by , on 17 June 2013

Due to lack of internet at the ISDB conference venue, it is not possible for the Node to tweet live from the conference. Instead we will try to post regular updates!

 

Cancun beachDay one of the International Society for Development Biology meeting, and boy is it hot here in Cancun! Not that anyone is complaining really- the Caribbean sea looks beautiful, and it is likely that conference attendees might be going for a morning swim before the morning sessions… not a bad way to do scientific conferencing!

The main conference started this afternoon, but many attendees arrived a few days earlier for the satellite symposium on the establishment and breaking of the left-right axis in development and disease. This will be the topic of a later post.

The conference started with a Presidential symposium packed full of interesting talks. Alejandro Sanchez Alvarado kicked off the event with a talk about his research on planaria. These little organisms have amazing regenerative properties, and this ability relies on the presence of adult stem cells called neoblasts. A lot of his talk, however, focused on the unusual embryogenesis of planarian which includes, among others, a yolk localized on the outside of the egg! He also suggested that maybe in the age of molecular biology we might need to develop a new vocabulary to describe embryological processes.

The next speaker was Celest Nelson. Cells in the developing embryo not only apply forces to their neighbors but are also exposed to a complex mechanical environment (e.g. surrounding fluids or contracting movements of nearby tissues). Her lab uses both experimental biology and computer modeling to address how some of these forces can influence processes such as the branching of the lung. The interplay between mechanical forces and known chemical and genetic pathways was also the topic of a later talk by Elliot Meyerowitz. He focused on how patterns are established in the formation of plant meristems, and his talk included beautiful images of meristems.

Elly Tanaka described the work of her lab and others on how the mechanisms of muscle regeneration following limb amputation varies between salamander species. Finally, James Sharpe talked about his work combining advanced imaging with computational modeling to understand how vertebrate limb shape is achieved.

In addition to the great talks, one of the highlights of the first day was actually in the RIKEN institute booth. Up for collection were beautiful postcards of model organisms portrayed in the style of traditional Japanese decorative arts. You might remember an older post by Eva where she first mentioned these beautiful designs, and which included a link to a page where you can download them. Following the tradition of bringing developmental biology and Japanese traditions together, members of the RIKEN institute were also distributing developmental biology-themed origami! In beautiful Japanese patterns, and including instructions on how to make your own model organism, these were definitely very popular! If you are at the meeting, this is definitely one to collect. Alongside, of course, the Node tea bags! Although the hot weather here in Mexico means that you might have to wait to drink it until you get back to the lab…

P6160049 smaller

dev bio origami 1

dev bio origami 2

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ISSCR Annual Meeting – Day 3

Posted by , on 16 June 2013

After a fun night socialising, the stem cell science kicked off again in earnest on Friday morning. The morning session turned to ‘Cell and Gene Therapy’ – the final goal of many at the meeting. David Williams and Alesandra Biffi provided fascinating insights into the past and future of the gene therapy field, with a particular focus on gene delivery using haematopoeitic stem cells (HSCs). It’s good to see that the gene therapy has had somewhat of a resurgence in recent years, in part due to its interface with stem cell biology. The ethical dilemmas that these experimental therapies undoubtedly raise were summarised and expanded upon by Nancy King, while Sarah Ferber described a different approach to regenerative medicine, detailing her work on transdifferentiation of liver to pancreas as a potential therapy for diabetes. The final talk of the morning plenary came from Charles Murry who works on cardiac regeneration. He described the challenges – financial, practical and scientific – of using the non-human primate (NHP) as a model to study cell therapy for cardiac disease. Indeed, throughout the conference there have been frequent discussions about how we can properly characterise human pluripotent cells and their derivatives, and many have expressed the opinion that validating findings in the NHP is an important step. Murry’s contribution certainly focussed the debate on both the trials and benefits of such an approach. The sight of human ES cell-derived cardiomyocytes integrating and apparently functioning in vivo in the NHP heart was certainly a very exciting end to the morning plenary– regardless of your stance on NHP research.

The concurrent sessions included epigenetics, HSCs, chemical conrol of stem cell behaviour, organ development, stem cell therapies and germ cell biology. The two main speakers in the germ cell session were presenting on haploid ES cells – an exciting new tool in stem cell biology. Jinsong Li provided a good overview of the field and his own work in the mouse system, before describing the successful derivation of NHP haploid ES cells.  Josef Penninger focussed on the application of mouse haploid cells for genetic screens and his belief that ‘yeast genetics’ is now possible in mammalian cells. He also plans to make the powerful platforms his lab has developed accessible to the whole community – a massive undertaking for which he deserves a great deal of credit. Robin Hobbs brought the focus back to germline developmental biology with his latest insights into Tsc2-mTORC1 signalling in spermatogonial stem cells and I was delighted to be able to share some of my work on the connection between pluripotency and the germline. Concurrent session 2 featured many more exciting presentations, including sessions on immunology, cancer and chromatin regulation – something for everything on another full day of science.

In the evening Shinya Yamanaka hosted the president’s reception at the lavish Harvard Club in town. In an entertaining speech he revealed that the phone call from Stockholm interrupted his attempts to fix his washing machine – ‘luckily I don’t have to do this any more’ he quipped!

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ISSCR Annual Meeting – Day 2

Posted by , on 15 June 2013

Day 2 featured a full scientific program, including a morning plenary and two afternoon sessions with concurrent talks running in five different rooms. Luckily many of the talks are being videoed and will be available to attendees for a few weeks after the event – a good idea as it’s impossible not to feel like you’re missing exciting science even with the most careful scheduling.

We kicked off with a disease modelling session, certainly a popular topic which has also featured in many posters and short talks throughout the conference so far. It is clear that many labs and institutions are investing huge efforts in collecting and cataloguing induced pluripotent stem (iPS) cells from patients with a vast array of different diseases. The plenary talks from Lawrence Goldstein, Haruhisa Inoue and Joseph Wu focussed on using iPS cells to interrogate the pathogenesis of amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and cardiovascular disease. The general consensus was that the standard of the presentations was very high, really raising the bar of what can be achieved even when modelling complex diseases in the dish. Ludovic Vallier also presented his lab’s efforts to understand genetic and phenotypic variability in a large cohort of iPS cell lines derived using different tissues of origin and reprogramming methods. iPS cells were also well represented in the concurrent session on pluripotency and there remains a great deal of interest in the mechanism of reprogramming. A particularly noteworthy talk by Jacob Hanna presented incredible data demonstrating that knocking out one component of a chromatin remodelling complex can lead to 100% reprogramming efficiency on expression of the Yamanaka factors. The cell fate conversion session featured talks on ‘direct reprogramming’ (or trans-differentiation) emphasising not only how malleable cell fate is, but also the challenges in manufacturing fully functional, terminally differentiated cell types in vitro. Indeed, some discussions have focussed on whether this is necessary or even desirable in all contexts – as long as cells can safely and efficiently ‘do the job’ asked of them. The idea of completely new cell types is certainly intriguing, although maybe not to the developmental biologist still struggling to understand the cells we have already! On a related note, Pentau Liu presented his lab’s work on designer transcription factors which are custom made to turn your gene of interest on or off. Certainly a neat trick which sparked debate as to how one might utilise these in the future to answer different biological questions. Other sessions included neural stem cells, tissue engineering, stem cell signalling and niches, aging and metabolism, and ‘new technologies’ to name but a few. Each concurrent session has also featured poster teasers which are an excellent recent addition to many conferences – one speaker even used their allotted time to sing/rap about their work. I’m sure this poster got plenty of foot traffic… although I’m not convinced this approach will, or should (!), necessarily catch on!

The day ended with a social event for young investigators at a local Irish bar – although even the more senior scientists who sneaked in couldn’t resist the lure of the dance floor! I won’t name any names… but the blood stem cell field was certainly well represented!

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The Node at the ISDB

Posted by , on 14 June 2013

Are you attending the ISDB meeting starting this sunday in Cancun, Mexico? If not, don’t worry- the Node will be there, and we will be tweeting using the #ISDB2013 hashtag. If you are not a Twitter user, Cat will also be posting updates from the meeting here on the Node, so that is another way you can follow the conference!

If you are going, then why not say hello? Cat will be at the Company of Biologists booth (Booth 10) quite a lot of the time with some Node freebies (including our tea bags!), but feel free to chat to her if you see her around elsewhere. It would be great to meet some of you, and find out about what you think about the Node. Hopefully see you there!

 

The Node mexican logo 2

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Seeing a future for retinal regeneration

Posted by , on 14 June 2013

retina 2013Regeneration is a superpower not just reserved for superheroes—salamanders and newts are able to regenerate lost limbs and tails, and fish can regenerate new retinal neurons after injury to the eye.  Mammals have limited ability to regenerate retinal neurons, but a recent paper in Development finds that a single transcription factor may be able to change that.

In fish, chemical- or light-induced damage to the eye’s retina drives retinal neuron regeneration.  In this pathway, Müller glial cells re-enter the cell cycle and de-differentiate into multipotent progenitor cells able to differentiate into any type of retinal neuron.  The transcription factor Ascl1 (Mash1 in mammals) is upregulated shortly after injury, and is required for retina regeneration.  Mammals do not upregulate Ascl1 after injury, and have a limited ability to regenerate injured retinal neurons.  A recent study in Development investigated if ASCL1 alone could induce the retinal neuron regeneration pathway in mammals.  Pollak and colleagues overexpressed Ascl1 in mouse Müller glial cells and intact retinal explants, and found that ASCL1 upregulated retinal progenitor genes and downregulated glial genes.  ASCL1 remodeled chromatin at the transcription factor’s targets to a more active configuration.  These ASCL1-reprogrammed cells have several characteristics of neurons, including morphology and physiological response to neurotransmitters.  In the images above, Müller glial cells (green) in entire retina explants treated to overexpress Ascl1 (bottom row) re-entered the cell cycle (red, arrowheads).  Control retina explants are in the top row.  From these results, Pollak and colleagues suggest that ASCL1 overexpression may provide a strategy for repair of the retina after injury or disease in humans.

For a more general description of this image, see my imaging blog within EuroStemCell, the European stem cell portal.
ResearchBlogging.orgPollak, J., Wilken, M., Ueki, Y., Cox, K., Sullivan, J., Taylor, R., Levine, E., & Reh, T. (2013). ASCL1 reprograms mouse Muller glia into neurogenic retinal progenitors Development, 140 (12), 2619-2631 DOI: 10.1242/dev.091355

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Post-Doctoral Research Associate (Transcriptional Control of Stem Cell Fate) x 2

Posted by , on 14 June 2013

Closing Date: 15 March 2021

The Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute draws together outstanding researchers from 25 stem cell laboratories in Cambridge to form a world-leading centre for stem cell biology and medicine. Scientists in the Institute collaborate to generate new knowledge and understanding of the biology of stem cells and provide the foundation for new medical treatments.

The Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge provides outstanding scientists with the opportunity and resources to undertake ground-breaking research into the fundamental properties of mammalian stem cells.

Postdoctoral Research Associate x2 – Transcriptional control of stem cell fate

Applications are invited for two postdoctoral positions to investigate the molecular control of embryonic stem cell lineage commitment and differentiation. One will be part of the European Commission 7thFramework Programme Project “4DCellFate,” and will focus specifically on the role of the NuRD complex in processes determining cell fate. The second is funded by the Wellcome Trust and will focus more generally on transcriptional processes controlling lineage commitment of pluripotent cells.

For either position demonstrated experience in the analysis of transcriptional and developmental mechanisms will be required. The candidate is expected to have considerable expertise in molecular biological and biochemical techniques. Previous experience in early mammalian embryogenesis, stem cell biology, transcriptional dynamics and/or chromatin biochemistry is highly desired. The position will be in the Transcriptional Control of Stem Cell Fate Group and is available immediately.

You should have been awarded a PhD degree or equivalent and have several years laboratory experience.

To apply, please visit our vacancies webpage:

http://www.stemcells.cam.ac.uk/careers-study/vacancies/

Informal enquiries are also welcome via email to: Dr Brian Hendrich Brian.Hendrich@cscr.cam.ac.uk or to cscrjobs@cscr.cam.ac.uk

These positions are available for 2 years in the first instance.

Applications must be submitted by 17:00 on the closing date of 14th July 2013.

Interviews will be held week commencing 29th July 2013. If you have not been invited for interview by 25th July 2013, you have not been successful on this occasion.

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The 6th International EMT Meeting

Posted by , on 14 June 2013

The 6th biennial meeting of the EMT International Association (TEMTIA) will be held in Alicante, Spain, Nov. 13- 16, 2013.

For information and registration, please visit www.emtmeeting.org.

Special sessions will include Developmental EMT/Cell Mol Biol of EMT/Cancer and EMT/Stem cells/Modelling, etc.

 

Earlybird registration is available until July 31st

There will be a number of travel awards and poster prizes, and that at least 2 slots have been retained in each session for talks selected from abstracts.

A special Betty Hay award will be chosen to support a young female scientist who has established her laboratory within the last 5 years.

Please check the website for award criteria and application process.

 

Please pass this on to anyone who may be interested.

Looking forward to seeing you in Alicante!

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ISSCR Annual Meeting – Day 1

Posted by , on 13 June 2013

Wow. Big conference

Over four thousand stem cell biologists were welcomed by Nobel Laureate and ISSCR President Shinya Yamanaka in the opening address of the 11th Annual Symposium of the International Society for Stem Cell Research, and in a hall with 8 huge screens beaming the plenary lectures across a massive conference hall it certainly felt like the whole international stem cell community was in attendance. Clearly, stem cell biology is a broad church and this was certainly evident from the talks on Day 1 which included old-school developmental biology, cancer biology, hardcore in vivo imaging, single-cell tracking, tissue homeostasis, epigenetics, regenerative medicine, basic cell biology and political intrigue as well.

James Thomson opened proceedings with a talk concentrating on the political and financial challenges that accompanied his quest to derive human embryonic stem (ES) cells, a stark reminder of the unique ability of stem cell biology to break ethical as well as scientific boundaries. Doug Melton provided a clear and thought provoking update on his lab’s quest to make physiologically relevant pancreatic beta cells and Edith Heard gave an interesting talk looking at the reciprocal relationship between pluripotency and X-chromosome reactivation. Rick Young presented his recent work on ‘super-enhancers’ while Elaine Fuchs delivered the Anne McLaren Memorial Lecture with aplomb, detailing her lab’s pioneering work on skin stem cells.
With 20 minute slots the talks were short and sharp, it was certainly interesting to see the big names forced to deal with the ‘short talk’ format usually reserved for post-docs and graduate students. Surprisingly there was no time available for questions, which was a shame as many were raised. I was slightly nervous that this would set the tone for the rest of the day, with presidential addresses and no chance for discussion or debate, which for me is the whole purpose of attending a conference. However, the second session reverted to a more standard format; still fantastic talks from top scientists, but with time for questions from the floor and more interaction. The overall theme shifted towards imaging technology and the importance of single cell analysis. Charles Lin demonstrated just how far the current live cell imaging technology can be pushed by those seeking to ask important in vivo questions about stem cell behaviour, Paul Frenette detailed his lab’s work to characterise the haematopoietic stem cell (HSC) bone marrow niche and Tim Shroeder gave an excellent account of how much can be learned just by ‘looking’ carefully at in vitro cell behaviour. He certainly showed provocative data regarding the concepts of bistability and heterogeneity both in the blood and pluripotent stem cell systems. George Daley rounded the day off with a talk which demonstrated that stem cell biology and developmental biology are one and the same thing – with the focus on his particular interest in developing in vitro HSC technology.
The ensuing poster session only served to emphasise the sheer scale of the meeting, with posters as far as the eye could see. Where to begin? However, the free bar certainly got the creative juices flowing and many discussions spilled over into Boston’s many night spots. Needless to say I was a little ‘tired’ this morning but I’ll try and find out if I missed any major advances in iPS cell disease modelling (this morning’s plenary session). The afternoon will proceed with concurrent sessions – pluripotency for me – which will be larger than many normal conferences! Hopefully there will be more fantastic science to update you on tomorrow.
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Biologically Inspired Digital Designs

Posted by , on 13 June 2013

Birds in flight were an inspiration for Wright brothers to build aeroplane. Be it how Geckos scurry up walls or sub cellular trafficking of molecules, fundamental biological phenomena are always been a greater source of inspiration for new technological innovations.

Recently, I came across two different articles in Nature and Science published almost during same week describing two technologies inspired by insect vision and flight. When I read Zoology major for my previous degrees, I was exposed to great deal of insect physiology and I was always intrigued by their compound eyes that are formed of thousands of units or lenses (ommatidia) which are helpful to view in large angle and detect fast movements.

A remarkably sophisticated optics in nature is Arthropod vision. Inspired by this biological phenomenon, Song et al., published building of digital camera with a lens that resembles Arthropod compound eye. The authors have constructed 180 tiny lenses on a elestomeric (can change from planar to hemispheric geometry) sheet, something same as the eyes of fire ants and bark beetles. The strategy is used to build apposition eye type camera but the same can be applicable to other different vision types of insects such as superposition eyes. Apparently this technology would enable to generate advanced surveillance devices, tools for miniaturized endoscopy and other demanding applications.

(Image adapted from http://www.nature.com/nature/journal/v497/n7447/full/497047a.html)

Insects also have evolved to have remarkable flight characteristics and are the only group of invertebrates to have flight ability. Fifteen years of work by Ma et al., have enabled to build a tiny robot flight, inspired by insect aerodynamics. They have developed an 80-milligram at-scale robotic flight with piezoelectric flight muscles overcoming sever miniaturization challenges. They have used Diptera (flies) as model system due to their simple wing anatomy and exemplary aerial agility. The robotic fly they have developed is tethered to a battery and autopilot. But, cordless microrobot flies are not impossible in future with radically new battery technologies. This robofly is a best example of out-of-fiction devices and would be helpful for studying insect-scale, flapping-wing flight mechanics and flight control. See the cool video of the robot in action – here

The bunch of authors from both studies seems to have background in engineering and technology. But, to realize their idea on biomimetics and come up with these impending technologies, they had to refer several research works in the field of Zoology, especially on insect visual mechanisms, physiology and aerodynamics. In recent years researchers starting to appreciate these kind of cross-disciplinary approaches, which are indeed essential for envisaging big picture science.

 

Song et. al., Digital cameras with designs inspired by the arthropod eye. Nature 497, 95–99

Ma et. al., Controlled Flight of a Biologically Inspired, Insect-Scale Robot. Science 3 May 2013: Vol. 340 no. 6132 pp. 603-607.

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