Last week the International Society for Stem Cell Biology meeting took place in Stockholm, and next week is the turn of the Society for Developmental Biology meeting, in Utah.  However, an annual meeting is not the only thing that a society may do. Other activities can include, for example, the publication of a peer-reviewed journal, advocacy for science funding, outreach/and or education of the public and its members, or the creation of networking opportunities. Are all of these useful? Do they play a role in your decision to become a member of a society? This month we are asking:

What is the role that scholarly societies play or should play in the community, and how important are they?

Share your thoughts by leaving a comment below! You can comment anonymously if you prefer. We are also collating answers on social media via this Storify. And if you have any ideas for future questions please drop us an email!

(1 votes)

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Elena Boer, Shun Sogabe and Joe Hanly are currently attending the MBL Embryology course in Woods Hole MA.

2015 marks the 122nd year of the Woods Hole Embryology course. This program has a long and prestigious history, as exemplified by the long list of alumni who grace the the wall of class photos in the lab. A quick scan of these photos reveals many of our own supervisors (in some version of their younger selves), a few Nobel Prize laureates, and quite a few of the PIs and TAs who have returned to teach the course this year. This year’s class is made up of 24 students from diverse backgrounds, representing 22 institutions and 14 different nations. To support our crazy 6-week journey through the depths of embryological research, we are equipped with a variety of compound, confocal, and light sheet microscopes (rumored to be worth around $3 million), as well as buckets and buckets of amazing reagents and equipment. We start our days with three and a half hours of lectures and in-depth discussions, and then hit the lab for demonstrations and independent experiments which frequently run until midnight or later.

We’re now at the end of week 2 of 6. Are you wondering how it is physically possible to maintain such a schedule and keep your sanity? Well, after some preliminary experiments, we suggest that you probably can’t. We are so tired, we can hardly type these worfs. Indeed, we’ve been writing this blog in the brief breaks we get whilst washing out antibodies. Since our arrival in Woods Hole on June 6th, we’ve been hard at work for 15-18 hours a day, 6+ days a week. The only thing keeping us awake is the sheer joy and camaraderie that comes from being in such an intellectually stimulating place with so many great people. And coffee. Lots of coffee.

Many of us arrived in Woods Hole the day before the course began and had a chance to start getting to know each other during an informal tour of Woods Hole and dinner at Quick’s Hole, followed by drinks at the Kidd, the best (a.k.a. only) bar in town. At our first official course dinner the following night, Alejandro and Richard (the course directors) threw us a curveball; after just meeting each other, we were split off into pairs and had to learn enough about the other person in 10 minutes to introduce them and their research to the group. Although this was a slightly terrifying experience, it set the tone of the course: intense, but not to be taken too seriously. This mentality has continued throughout these first two weeks, providing us with the opportunity to both learn and have as much fun as we’d like while being free from the stresses and constraints of our day-to-day research.

To make extra sure we weren’t taking things too seriously, the directors and course assistants planned a scavenger hunt on our first weekend, which involved teams of four dressing up as an assortment of marine animals and running around Woods Hole like crazy people – it’s fair to say we attracted a lot of attention. Many of us anxiously over-prepared for our first “Show and Tell” at the end of Week 2 as well, just to find out that the presenter would be wearing a silly hat and the audience would be supplied with small plastic balls to throw at the speaker if they went over their 3 minute limit. The relaxed environment manifests in other ways; for example, lots of quotable quotes have made it on the whiteboard in the breakroom. Our personal favorite so far: “RNAi is like a cheap date – what you really want is a long-term relationship with a mutant” (Dave Sherwood). For three meals a day, all participants, TAs, CAs and faculty stick together. Science is everywhere, but it is supportive and social. Alejandro and Richard are participating too. Every night, a few of us also get the opportunity to go out to dinner with the lecturer of the day. This seemed intimidating at first, but always turns out to be a really fun and relaxed experience filled with fascinating stories and often giving us great advice for our future research and careers.

So far, we have had a chance to work on sea urchins (L. variegatus), sea stars (P. miniata), nematodes (C. elegans), chicks (G. gallus), and mice (M. musculus). In the “zoo lab” last week, we were also given a variety of vertebrate embryos to dissect (e.g. chameleons, snakes, lizards). Each module has been exquisitely coordinated by a great team of people, who have kept the lab stocked with everything we need (i.e. reagents, equipment, embryos of different strains at various stages of development, etc.) This allows us to simply show up every day and do fun science. Most of us know someone who has taken the course in the past, therefore we all had an idea of what to expect from lectures and experiments. What we weren’t expecting was the way we are being molded as scientists through such amazing supervision. In our second week, for example, Claudio Stern gave us a quick tour through the history of developmental biology, and also led us through an enlightening discussion of experimental design. We were given the chance to propose our own experiments and get critical feedback from some of the leaders of the field. This not only reaffirmed our respect towards our predecessors and the field of biology as a whole, but also gave us a clearer image of what it means to do “good science”.
For most of us, the primary goal is to absorb as much information as possible while we are here. Because there are no deadlines to meet and no papers to publish, it is an incredibly liberating (and fun!) environment to be living and learning in.Two weeks in, we already know that we are going to come away from this experience as very different people.

—–

Elena is a recent PhD graduate from Rod Stewart’s lab at the Huntsman Cancer Institute/University of Utah in Salt Lake City, Utah. This fall, Elena will be making the move from neural crest migration in zebrafish to evolutionary genetics in pigeons when she starts as a postdoc in Mike Shapiro’s lab at the University of Utah.

Shun is a PhD student in Bernie Degnan’s lab in the School of Biological Sciences at the University of Queensland, Australia. He studies the ontogeny of choanocytes (feeding cells) in the sponge and their involvement in the sponge stem cell system.

Joe is a PhD student in the lab of Chris Jiggins in the Department of Zoology at the University of Cambridge, UK. He studies the development and evolution of the wing patterns of Heliconius butterflies.

—–

A few photos from the first two weeks:

Collection of prints and manuscripts in the Woods Hole Library

An early edition of On The Origin of Species, signed by Charles Darwin.

Learning how to load the Zeiss Light Sheet Microscope

Some of the stations in our “Manipulation Room”, fully equipped for microinjection, electroporation and microsurgery.  

Alejandro presenting his findings at our first Show and Tell, wearing the obligatory Sea Dragon hat. 

THE LAB, WHERE ALL THE MAGIC HAPPENS. YES THIS IS ALL SUPPOSED TO BE IN CAPS. THATS JUST HOW EXCITED I AM ABOUT THE LAB. – Joe

(10 votes)

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We will be doing some maintenance work on the Node this Wednesday the 1st of July, and unfortunately this means there will be no access to the site then. You can expect the Node to be down from 7 a.m. (British Summer time) for up to 4 hours. We are sorry for the disruption, especially for those Node readers in Asia and Oceania. We will be up and running again as soon as we can, and with an exciting surprise!

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A really interesting recent paper on bioartificial limbs underscored the prospect of transplantation for problems in regenerative medicine. One key issue facing transplant technology is establishing appropriate innervation to the host. What factors control the amount of nerve emanating from an organ graft and the paths that this innervation takes? Alongside the familiar diffusible signaling factors and extracellular matrix components functions another important signaling modality: bioelectricity.

The ability of nerves to respond to physiological-strength extracellular electric fields has been long known.  My lab studies a different aspect of bioelectricity: signaling via endogenous resting potentials across the plasma membrane of all cells (not just neurons). We have found that the spatial distribution of these voltage states (anatomical Vmem gradients) are instructive influences for stem cell function, regenerative response, organ-level reprogramming, and metastasis.  Recently however, we used the Xenopus laevis embryo model to show another role for bioelectric gradients – the control of ectopic innervation.

Douglas Blackiston, a post-doc in our group, was interested in the plasticity of the brain. He showed that ectopic eyes transplanted to the sides of tadpoles enabled the resulting animals to learn in behavioral assays even when the primary eyes were absent. Apparently the brain had little difficulty recognizing an ectopic organ on the animal’s back as providing useful visual data; the tadpole brain was able to adjust its behavioral programs as needed, despite the fact that this was a novel anatomical configuration (not experienced during evolution) and that the eye became connected to the spinal cord, not the brain.

Transplanting eyes from RFP-labeled hosts allowed us to see the optic nerves emanating from the transplanted eye; normally there was just one or two main fibers.

The big surprise came when he used a technique we had previously developed for the study of bioelectrically-induced melanoma to depolarize a fraction of cells in the host animal. This strategy relies on the use of a drug that opens chloride channels and allows negative ions to leave cells expressing that channel, thus depolarizing them. When eyes were transplanted into hosts depolarized by this method, instead of one major nerve bundle we observed a massive innervation. A set of molecular-genetic experiments using Doug’s meticulous transplantation assay further showed that:

• 1) the host’s endogenous innervation did not change after depolarization: depolarization appears to be a signal that is particularly attended to by neurons that somehow know they are not in their normal location; but,
• 2) eyes grafted to their normal location did not hyperinnervate, suggesting that merely being surgically perturbed is not sufficient to fool these cells.
• 3) whether the eye came from the same animal or a different donor made no difference: this was not an effect based on self/not-self detection.
• 4) a range of methods (using chloride, potassium, or sodium) could be used to induce or rescue hyperinnervation, demonstrating that the phenotype is not an off-target effect of the drug, nor dependent on that one particular channel or even the chloride ion: the cells are sensitive to Vmem itself, regardless of which ion is used to achieve it.
• 5) depolarizing the donor eye did not induce hyperinnervation, suggesting that this is a non-cell-autonomous effect: the cells are reading the surrounding environment’s Vmem levels, not their own, in making growth decisions.
• 6) The ability of neurons to respond to depolarization of their neighbors required 2 things: serotonergic signaling through 5HT-R1,2, and gap-junctional communication.

These data suggested a model of the movement of serotonin among cells via gap junctions, under control of bioelectric gradients, as a signal that regulates neural extension and pathfinding. In this aspect, these data are similar to previous findings that bioelectric control of serotonin and gap junctional connectivity regulates left-right patterning, metastasis, and tumorigenesis. However, they raise numerous new questions. First, precisely how do neurons know when they are in the wrong location – what mechanism allows just the ectopic nerves to overgrow, leaving endogenous innervation completely normal? Second, what is the encoding used by the transmitted serotonin – are absolute levels important, or is the movement pulsatile (rate encoding), or spatially-patterned? The latter issue is especially difficult to address at this time because serotonin is too small to be fluorescently labeled without drastically affecting its movement through transporters and gap junctions. Finally, could strategic misexpression of ion channels, serotonergic transporters, and gap junction proteins be used to allow fine control of neural connectivity in transplantation contexts? New advances in developmental optogenetics, together with existing tools developed by labs working on neurotransmitter signaling, could allow sculpting of nerve growth from transplanted organs, whether bioengineered or harvested from living hosts.

Since Vmem regulation and serotonergic signaling appear to be involved in guidance of mammalian neurons as well, these data likely have implications for biomedicine. Indeed, a plethora of ion channel drugs exist, many of which are already approved for use in human patients for other indications. These form an “electroceutical” toolkit which could be richly exploited for the control of neural and other cell behavior in regenerative medicine and bioengineering.  Our lab is currently working on this goal in several models, as well as investigating the cognitive (behavioral) implications of massively increasing neural connections from transplanted sensory organs in Xenopus. Stay tuned!

(6 votes)

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Salamanders are remarkable organisms. Following the amputation or loss of complex structures such as parts of their eyes, hearts and brains, tails -including the spinal cord-, jaws and even full limbs, they are able to set up a regeneration programme which leads to the exact replacement of the missing structure, even as adults. As such, salamanders are considered the champions of regeneration. And, if the ability to regrow a full limb during adulthood was not surprising enough, they are able to do this over and over again, as their regenerative abilities do not decline as they age -unlike in most other organisms, including humans. This notable characteristic of salamander regeneration was recently demonstrated by an elegant experiment carried out by Goro Eguchi, Panagiotis Tsonis and co-workers¹, who systematically removed the lens of a cohort of newts 18 times during 16 years and showed, in a nutshell, that the resulting lens was almost identical to a young lens that has never regenerated. Hence, the regeneration process in these organisms can withstand the test of time. But, how is this possible? I recently set out to address this question and found that the answer may lie in a highly efficient mechanism of eliminating senescent cells².

Cellular senescence is a process by which cells that have been exposed to various types of DNA damage, telomere erosion and oncogenic stresses undergo a permanent withdrawal from the cell cycle. Like apoptosis, this cellular mechanism prevents the transmission of damaged genetic material, constituting a powerful anti-tumourigenic strategy. Unlike apoptosis however, it does not lead to cell death but to cells which are metabolically active and that can modify their microenvironment -through the acquisition of a senescence-associated secretory phenotype comprising growth factors, cytokines and matrix-remodelling proteins-, sometimes for the worse. Indeed, in recent years it has become clear that senescent cells can have detrimental effects on biological processes. This is particularly relevant to Ageing, as most organisms accumulate senescent cells during their lifetime, leading to a number of age-related disorders³. More recently, cellular senescence has also been linked to the age-related decline of regenerative abilities seen in mammals⁴. Given that such decline is not seen in salamanders, could it be possible that these organisms possess mechanisms to curtail cellular senescence?

To tackle this problem, the first requirement was to find a way of identifying senescent cells within salamander cells and tissues. Luckily, at that point we had already embarked on a project to investigate the roles of the tumour-suppressor p53 in regeneration⁵. With my DNA repair background, I couldn’t overlook the fact that p53 is a well known inducer of cellular senescence upon DNA insults and hence took advantage of this to find ways of inducing and detecting cell senescence in salamander cells, such as the well-established senescence-associated beta galactosidase staining. This allowed us to probe some interesting questions, starting with whether senescence occurs at all in salamanders. The short answer is yes, though very few senescent cells are present in normal tissues. In contrast –and quite unexpectedly- we found that they are strongly induced during limb regeneration. But, by the time the limb had regenerated, those senescent cells were gone. Interestingly, we did not detect any senescence induction during normal limb development, indicating that this phenomenon of induction and disappearance is specific to regeneration.

Given the high percentage of senescent cells induced in each round of regeneration, an initial hypothesis was that repetitive amputations should lead to an increase in the number of senescent cells in the regenerating structure. However, as foreshadowed above, this was not the case, with no senescent cells remaining even after five rounds of regeneration. In addition, and even more surprisingly, we found no age-related increase in the percentage of senescent cells in normal salamander tissues, in contrast to observations in most other organisms. This suggested that effective mechanisms of senescent cell clearance operate in salamanders, in normal and regenerating tissues. To test this further, we took advantage of the suitability of the salamander system for implantation experiments, and found that implanted senescent cells were selectively, efficiently and rapidly cleared from normal and regenerating tissues. Hence, the obvious next step was to characterise the clearance mechanism.

At the time, evidence was starting to emerge supporting a role for the immune system in eliminating senescent cells in certain pathological contexts. Therefore, we decided to probe whether the immune system, and in particular the macrophage, was part of the clearance mechanism. Using the well-established DiI and clodronate salt liposome system for labelling and depleting macrophages in vivo, we demonstrated that these immune cells are readily recruited to sites of either endogenous or implanted senescent cells, and that specific elimination of macrophages prevents senescent cell clearance within salamander tissues. Hence, this revealed that the macrophage is an essential piece of this effective immunosurveillance machinery. Ongoing studies are directed at characterising this mechanism further, both trying to determine its cellular components as well as the signals that mediate immune-senescent cell interactions – with a focus on the differences between salamanders and mammals. Clearly, unravelling this phenomenon will be important both from a basic science as well as a therapeutic perspective, as senescent cells have recently become therapeutic targets for the control of age-related diseases. Hence, salamanders could inspire strategies aimed at the efficient targeting of senescent cells for the promotion of healthy Ageing.

Overall, our work revealed that senescent cells are recurrently induced during regeneration of complex structures in salamanders and are subject to a strict mechanism of macrophage-mediated clearance (Figure 1). From a wider perspective, our findings have two important implications. First, that highly efficient mechanisms to eliminate senescent cells throughout lifespan do operate in certain species, and these –as in the case of salamanders- constitute interesting models for the study of senescence regulation and immunosurveillance. Second, that the transient induction of cellular senescence may play a positive role in regenerative processes, a provocative concept that is yet to be addressed.

Figure 1. Senescent cells are induced (by as yet unidentified stimuli) during salamander regeneration, where they may contribute to various aspects of this process. As regeneration proceeds to more advanced stages, senescent cells are cleared by an efficient mechanism of macrophage dependent immunosurveillance, which results in a regenerated limb devoid of senescent cells. This allows for the possibility of multiple rounds of regeneration through lifespan as well as avoiding the disadvantages of senescent cell accumulation.

Our observation that senescent cells are recurrently induced in regeneration was initially surprising, as cellular senescence is traditionally understood as a process with negative outcomes at the organism level. Indeed, from an evolutionary perspective, the persistence of cellular senescence as a genome safeguarding mechanism has been questioned many times: why would a damaged cell undergo senescence, whereby cells remain within the tissues and secrete factors that ultimately lead to their disruption, when it could simply be eliminated through apoptosis? Is it simply that its negative effects are felt during the post-reproductive period, and hence not selected, or is there another explanation? Emerging evidence supports the latter, as a number of studies suggest that senescent cells play positive roles in certain contexts. For example, recent reports support a role for cellular senescence in tissue remodelling during mouse development^6,7, as well as in wound closure⁸. Hence, it is possible that the senescent cells that are induced during regeneration could play important functions in this process – a hypothesis that I am addressing further. This research will not only shine new light into the process of regeneration, but into our understanding of the function, regulation and raison d’être of cellular senescence.

Max H Yun, PhD

Institute of Structural and Molecular Biology, University College London

LTRR-London Tissue Repair and Regeneration Meeting Series: www.ltrr.co.uk

References

1. Eguchi, G., Eguchi, Y., Nakamura, K., Yadav, M., Millán, J., & Tsonis, P. (2011). Regenerative capacity in newts is not altered by repeated regeneration and ageing Nature Communications, 2 DOI: 10.1038/ncomms1389

2. Yun, M., Davaapil, H., & Brockes, J. (2015). Recurrent turnover of senescent cells during regeneration of a complex structure eLife, 4 DOI: 10.7554/eLife.05505

3. van Deursen, J. (2014). The role of senescent cells in ageing Nature, 509 (7501), 439-446 DOI: 10.1038/nature13193

4. Sousa-Victor, P., Gutarra, S., García-Prat, L., Rodriguez-Ubreva, J., Ortet, L., Ruiz-Bonilla, V., Jardí, M., Ballestar, E., González, S., Serrano, A., Perdiguero, E., & Muñoz-Cánoves, P. (2014). Geriatric muscle stem cells switch reversible quiescence into senescence Nature, 506 (7488), 316-321 DOI: 10.1038/nature13013

5. Yun, M., Gates, P., & Brockes, J. (2013). Regulation of p53 is critical for vertebrate limb regeneration Proceedings of the National Academy of Sciences, 110 (43), 17392-17397 DOI: 10.1073/pnas.1310519110

6. Muñoz-Espín D, Cañamero M, Maraver A, Gómez-López G, Contreras J, Murillo-Cuesta S, Rodríguez-Baeza A, Varela-Nieto I, Ruberte J, Collado M, & Serrano M (2013). Programmed cell senescence during mammalian embryonic development. Cell, 155 (5), 1104-1118 PMID: 24238962

7. Storer, M., Mas, A., Robert-Moreno, A., Pecoraro, M., Ortells, M., Di Giacomo, V., Yosef, R., Pilpel, N., Krizhanovsky, V., Sharpe, J., & Keyes, W. (2013). Senescence Is a Developmental Mechanism that Contributes to Embryonic Growth and Patterning Cell, 155 (5), 1119-1130 DOI: 10.1016/j.cell.2013.10.041

8. Demaria, M., Ohtani, N., Youssef, S., Rodier, F., Toussaint, W., Mitchell, J., Laberge, R., Vijg, J., Van Steeg, H., Dollé, M., Hoeijmakers, J., de Bruin, A., Hara, E., & Campisi, J. (2014). An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA Developmental Cell, 31 (6), 722-733 DOI: 10.1016/j.devcel.2014.11.012

(7 votes)

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Frontal section image of mouse embryo with liver marker showing two different liver precursor populations invading and migrating into two different liver lobes (Siyeon Rhee).

Continuing the effort to bring young developmental biology researchers in the Boston area together, in a similar vein to the Young Embryologist Network in the UK, and following on from our previous meeting, on June 18th the second YEN USA meeting was held at Harvard Medical School as advertised on the Node recently.

The first talk was given by Siyeon Rhee (or rather Dr. Siyeon Rhee, as he had just successfully defended his thesis!), a graduate student at University of Massachusetts Amherst in Kimberly Tremblay’s lab, talking about the role of Yin-Yang1 (YY1) in liver specification. He discussed, from his work in mouse, how YY1 is required for embryonic development, in maintaining VEGF in the visceral endoderm of the yolk sac (Rhee et al., 2013) and also explained his work demonstrating two spatially and temporally distinct waves of liver bud specification that lead to formation of distinct lobes in the liver (Wang et al., 2014). Siyeon is about to move to California to start a postdoc position.

Siyeon Rhee presenting his work.

The next talk was from Dr. Samantha Morris, a postdoc in George Daley’s Lab at Boston Children’s Hospital, who is also moving, on July 1st, to start her own lab in the departments of genetics and developmental biology at Washington University in St Louis. She spoke about her work and collaboration with computational biologists to assess cellular identity using network biology (Cahan et al., 2014a) and in particular, assessing the fate of cells in direct conversion protocols using CellNet (Cahan et al., 2014b) to directly test and improve direct conversion of cells from one differentiated state to another (Morris et al., 2014).

A graphical abstract of Sam Morris’ work.

Left, Samantha Morris presenting her work; Right, a close up of her diagram of typical developmental pathways illustrating the principle of direct conversion.

Sam’s written a review that covers the current technologies to reprogram cells (Morris and Daley, 2013). Sam went on to speak about her work progressing into the investigation of liver cell fates, which she will now take onwards in developing her own lab.

Please check out the website and get in touch if you’re interested – the next meeting will happen in September,  with the Node’s very own Cat Vicente speaking, so stay tuned for future updates!

References

Rhee S., Guerrero-Zayas M.-I., Wallingford M. C., Ortiz-Pineda P., Mager J., Tremblay K. D. (2013) Visceral Endoderm Expression of Yin-Yang1 (YY1) Is Required for VEGFA Maintenance and Yolk Sac Development. PLoS ONE 8(3): e58828. doi: 10.1371/journal.pone.0058828

Wang J., Rhee S., Palaria A. and Tremblay K. D. (2015) FGF signaling is required for anterior but not posterior specification of the murine liver bud. Dev. Dyn., 244: 431–443. doi: 10.1002/dvdy.24215

Cahan P., Morris S. A., Collins J. J. and Daley G. Q. (2014a) Defining cellular identity through network biology Cell Cycle 13(21): 3313-3314. doi: 10.4161/15384101.2014.972918

Cahan P., Morris S. A., Lummertz da Rocha E., Daley G. Q., Collins J. J. (2014b) CellNet: Network Biology Applied to Stem Cell Engineering Cell 158(4): 903-15. doi: 10.1016/j.cell.2014.07.020

Morris S. A., Cahan P., Li H., Zhao A. M., San Roman A. K., Shivdasani R. A., Collins J. J., Daley G. Q. (2014) Dissecting Engineered Cell Types and Enhancing Cell Fate Conversion via CellNet Cell 158(4): 889-902. doi: 10.1016/j.cell.2014.07.021

Morris S. A. and Daley G. Q. (2013) A blueprint for engineering cell fate: current technologies to reprogram cell identity. Cell Research 23: 33-48. doi: 10.1038/cr.2013.1

(4 votes)

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This is my first post for the Node, so I thought I would introduce myself a little bit…

I just finished my MSc in Experimental Psychology (Behavioural Neuroscience) and now I am striving towards becoming a science communicator. Although, I would like to share the research that I am interested in and was involved in, so here’s a glimpse:

I have an interest in the mechanisms underlying stress regulation, especially adult hippocampal neurogenesis. There is plenty of work published on the detrimental effects of stress on neurogenesis (See Review – Schoenfeld & Gould, 2012) in addition, at least one functional purpose for neurogenesis is stress regulation (Snyder et al., 2011). Chronic stress almost always suppresses neurogenesis (there are exceptions – see Hanson et al., 2011). However, acute stress is interesting in that there is conflicting evidence on its effects on neurogenesis. These differences may ultimately lie in the type of stressor used, although different results have manifested from the same protocol (Tanapat et al., 2001; Thomas et al., 2006).

Let’s take a step outside of the cellular/neuroscience world and into the more behavioural realm for just a moment:

I used an animal model for post traumatic stress disorder (PTSD) that was created by the late Bob Adamec which produces prolonged anxiety-like behaviour following the stressor. This model was unique in that very few labs in the world expose their rat subjects to an unprotected cat exposure (Adamec & Shallow, 1993)!

Image created by Catherine Lau

Much of the chronic stress research and neurogenesis work applies to stress and mood disorders. I wondered if there would be any effect on neurogenesis following a stressor that produces long lasting anxiety-like behaviour. In addition, an interesting review by Kheirbek et al., 2012 shows a potential link between PTSD and neurogenesis through pattern separation (differentiating highly similar contexts). In short, the review talks about how PTSD patients may have less newly born neurons available to differentiate similar episodes and therefore generalize, contributing to symptoms including the re-experience of the traumatic event in their mind. My results revealed that despite an evident stress response (as measured by corticosterone levels), neurogenesis was not different in the hippocampus between controls and predator stressed (Lau et al., manuscript in progress).

What’s happening? Here are some thoughts:

One immediate thought is adaptation, as a certain amount of stress is necessary to cope in our environments. But, how does this manifest in the brain? Kirby et al., 2013 reported an interesting result following acute stress (immobilization and foot shock). Instead of finding a decrease in neurogenesis, an increase in hippocampal neurogenesis was reported in the dorsal hippocampus due to increased secretion of astrocytic FGF2 (necessary proliferative factor for neural progenitor cells). This evidence demonstrates that acute stress may define a life-saving adaptation compared to long term pathology, by stimulating plasticity through increasing neurogenesis. Thus, new neurons in the hippocampus are perhaps needed during acute stress.

A difficult aspect to overcome in any experiment and also in mental health disorders is individual differences. The severity of the disorder may be different as well as how individuals respond to treatment. Some labs are tackling this problem by screening subjects before hand to group a vulnerable and resilient group. Rats displaying extreme behaviour in supposedly exploratory environments, such as the elevated plus maze (no time spent in open arms vs. closed arms) would be classified as the vulnerable group (Cohen et al., 2006).

In addition, there has also been interesting work done by Michael Meaney at McGill University attempting to look at the epigenetics behind depression and stress disorders. Individual differences were characterized by using the frequency of mother and pup interaction (licking/grooming behaviour). Offspring who had mothers giving a high amount of licking/grooming showed a reduced corticosterone response, as well as decreased startle and increased exploratory behaviour compared to those offspring who received less mother to pup interaction. By increasing grooming during their first week of life, rat mothers alter the DNA structure of the glucocorticoid receptor gene promoter in the hippocampus of their offspring (Meaney & Szyf, 2005). This evidence paves the way towards understanding risk factors in mental health, especially early life stressors and how they connect to mental disorders following childhood.

Although I am no longer involved in this area of research, I am trying my best to keep up to date with new experiments that will help elucidate the mechanisms underlying mental health disorders, such as depression and PTSD.

If anyone has interesting articles or thoughts about this, please let me know. Thank you!

References:

Adamec, R., & Shallow, T. (1993). Lasting effects on rodent anxiety of a single exposure to a cat Physiology & Behavior, 54 (1), 101-109 DOI: 10.1016/0031-9384(93)90050-P

Cohen, H., Zohar, J., Gidron, Y., Matar, M., Belkind, D., Loewenthal, U., Kozlovsky, N., & Kaplan, Z. (2006). Blunted HPA Axis Response to Stress Influences Susceptibility to Posttraumatic Stress Response in Rats Biological Psychiatry, 59 (12), 1208-1218 DOI: 10.1016/j.biopsych.2005.12.003

Hanson, N., Owens, M., Boss-Williams, K., Weiss, J., & Nemeroff, C. (2011). Several stressors fail to reduce adult hippocampal neurogenesis Psychoneuroendocrinology, 36 (10), 1520-1529 DOI: 10.1016/j.psyneuen.2011.04.006

Kheirbek, M., Klemenhagen, K., Sahay, A., & Hen, R. (2012). Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders Nature Neuroscience, 15 (12), 1613-1620 DOI: 10.1038/nn.3262

Kirby, E., Muroy, S., Sun, W., Covarrubias, D., Leong, M., Barchas, L., & Kaufer, D. (2013). Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2 eLife, 2 DOI: 10.7554/eLife.00362

Meaney MJ, & Szyf M (2005). Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome. Dialogues in clinical neuroscience, 7 (2), 103-123 PMID: 16262207

Schoenfeld, T., & Gould, E. (2012). Stress, stress hormones, and adult neurogenesis Experimental Neurology, 233 (1), 12-21 DOI: 10.1016/j.expneurol.2011.01.008

Snyder, J., Soumier, A., Brewer, M., Pickel, J., & Cameron, H. (2011). Adult hippocampal neurogenesis buffers stress responses and depressive behaviour Nature, 476 (7361), 458-461 DOI: 10.1038/nature10287

Tanapat, P., Hastings, N., Rydel, T., Galea, L., & Gould, E. (2001). Exposure to fox odor inhibits cell proliferation in the hippocampus of adult rats via an adrenal hormone-dependent mechanism The Journal of Comparative Neurology, 437 (4), 496-504 DOI: 10.1002/cne.1297

Thomas, R., Urban, J., & Peterson, D. (2006). Acute exposure to predator odor elicits a robust increase in corticosterone and a decrease in activity without altering proliferation in the adult rat hippocampus Experimental Neurology, 201 (2), 308-315 DOI: 10.1016/j.expneurol.2006.04.010

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StemCellTalks is a Canadian high school outreach initiative that has been running in 7 Canadian cities since 2010. This symposium was established to facilitate knowledge transfer between academia and high school students pertaining to the science and practical ethics of stem cells. To date, over 500 graduate student and trainee volunteers have reached over 5000 high school students.

This year, the Vancouver chapter of StemCellTalks partnered with the biotechnology company STEMCELL Technologies Inc. to offer three talented student bloggers – Danielle Cohen, Julie Cui, and Ryan Scott – the chance to blog about their experience at StemCellTalks Vancouver. Furthermore, they won the opportunity to visit STEMCELL Technologies Inc.’s Vancouver headquarters on June 19, 2015. Over the next few weeks, you will be able to find their blog posts about StemCellTalks Vancouver appearing on Let’s Talk Science’s website Curiocity, as well as another version of this blog post at the stem cell blog Signals. We are happy to share Julie’s post here on the Node!

By Julie Cui (Lord Byng Secondary School, Vancouver, British Columbia, Canada)

Dr. Bruce Verchere pulled up a slide of a not-too-flattering depiction of Dr. Timothy Kieffer on the overhead screens and the room full of high school students erupted in laughter. It was a good-humored and very academic debate about stem cell vs. pig islet treatments for diabetes, I assure you, and seeing their passion for their field was one of those truly inspirational moments that I knew would stay with me for a long time.

8 o’clock earlier that Friday morning found me among a group of sleepy but excited high schoolers huddled in the foyer of the Pharmaceutical Sciences Building at UBC. It was the StemCellTalks Vancouver Symposium!

Armed with just pen, reading glasses, and basic Biology 12 knowledge of how stem cells worked in differentiating into different types of body cells, I was ready to absorb all the information I could about stem cell research findings and how they could be applied to diabetes treatment specifically. In the following hours, through the wonderfully informative talks by Dr. Fabio Rossi (UBC Biomedical Research Centre) and Dr. Francis Lynn (Child & Family Research Institute) and of course, the passionate debate between Dr. Bruce Verchere (Child & Family Research Institute) and Dr. Tim Kieffer (UBC Life Sciences Institute), we learned all about the different types of stem cells and how already-specialized body cells could be turned back into induced pluripotent stem cells, which could then specialize into a different type of body cell that we want. We also learned about alternatives to stem cell treatments of diabetes, including transplanting functioning donor islets and pig islets into patients with diabetes to help them produce the insulin they need to regulate their blood sugar levels. But I took away from StemCellTalks so much more than my new-gained knowledge of stem cell biology and stem cell-based treatments.

As a high school student, I find that we rarely have the chance to hear about professionals in science-related fields other than academic researchers. hile learning about academic research is very cool and inspiring in itself, it was the range of professional perspectives that we were exposed to at StemCellTalks that allowed me to see the bigger picture of the whole process of research and treatment development. Science professionals are not just the lab workers, but also the ethics board members, the regulation makers and the industry officials. For me, the various speakers’ perspectives really drove home the point that only through the combined efforts of all the different professionals involved can a treatment be discovered, tested, and eventually approved for clinical application. They encouraged me not to feel limited to just one idea of a career, but to continue exploring the many different types of careers in science, opening a whole other world of opportunity.

The passion of everyone at the symposium was so wonderful and inspiring as well. Although I am from the City of Vancouver, during the small group discussions, I met peers who had travelled from outside of Vancouver to be there, from as far away as Abbotsford and Vancouver Island. Many of them had personal connections to diabetes, and every one of them was eager to learn more and make a difference. It was such a pleasure to talk to like-minded peers and university mentors and feel that, in a few years, we could be part of this effort to improve stem cell treatments for diseases such as diabetes. I was genuinely inspired at the symposium, and am very eager to learn more about real-world applications of the treatments. As one of the winners for StemCellTalks’ blogging contest, I’m very excited to have the chance to visit STEMCELL Technologies Inc. to learn the role of such a successful biotechnology corporation in bringing treatments and technologies to life. I very much look forward to meeting the people involved in this biotechnology company, experiencing the real biotechnology industry work environment, and sharing that experience in a blog post with my peers and science-professionals-to-be, of course. In closing, I just wanted to say thank you to everyone who made the truly memorable experience that was StemCellTalks possible!

@StemCellTalks
#StemCellTalksVan

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Join us for the 8th International Conference of the Latin American Society for Developmental Biology in the Port of Santos, SP, Brazil (October 20th-23rd).

We have a great line-up of speakers, a Genomic Editing and Analyses workshop, and a Comparative Embryology of Marine Invertebrate satellite course.

Abstract submission deadline is June 30th!!!  For more information check: http://lasdb2015.com/

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We’re really excited to be providing travel grants to support life science researchers and would like to share the opportunity with you. As a lot of us on the Axol team have an academic research background in the life sciences, we are really aware of how important funding to attend conferences is. To help, we are offering 2 x $1000 travel grants to allow the recipients to attend a life science conference of their choice in order to advance and share their research knowledge. All we ask in exchange is that you provide a blog post about your meeting experience!

To be eligible you must be a PhD student or postdoctoral researcher at a university or other non-profit organisation performing life science award.

The deadline for the 2015/16 travel grant application is 30th June 2015. 

Find out how to apply here: http://www.axolbio.com/page/travel-grants

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