Developmental Biologists welcome!

Teaching & Scholarship Lectureship in Biology/Zoology

Details on https://jobs.bangor.ac.uk/

Job Number: BU00940
School/Department: School of Biological Sciences
Grade: 7
Salary Information: £31,342 – £37,394 p.a on Grade 7
Contract Duration: Permanent

Closing Date: 19-08-2015

The School of Biological Sciences wishes to appoint a Lecturer (Teaching and Scholarship), to assist in the development of our dynamic and growing school. Applications are particularly sought from outstanding individuals with teaching and scholarship strengths in the Biological sciences. In the last 4 years our undergraduate intake has increased we now recruit over 200 undergraduates onto our biology and zoology degrees per year and we have introduced new programmes at undergraduate and Masters level. To support this expansion, we have recently appointed nine academic staff, and we are currently seeking 3 more lecturers for mainly research-led posts. We are inviting applications for a new Teaching and Scholarship post to help enhance and develop the curriculum in our existing degree programmes, which are focussed around Zoology and Biology.

Bangor University is committed to excellence in teaching & scholarship and offers attractive career prospects for staff with such expertise.

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Developmental Biologists welcome!

Details on https://jobs.bangor.ac.uk/

Lecturer in Biology/Zoology (3 posts)

Job Number: BU00844
School/Department: School of Biological Sciences
Grade: 7 or 8
Salary Information: £31,342-£37,394 (Grade 7); £38,511-£45,954 (Grade 8) p.a. depending upon experience

Contract Duration: Permanent

Closing Date: 10-08-2015

The School of Biological Sciences invites applications for three permanent Lectureships in the broad area of Biology encompassing the full spectrum of genes, organisms and ecosystems. As part of the College of Natural Sciences, we are a dynamic and growing School with a strong research record and successful recruitment onto our undergraduate and postgraduate degrees. Currently we are looking to expand our research base, and our teaching and outreach capabilities. Bangor University is committed to excellence in research, teaching & scholarship and offers attractive career prospects for staff with such expertise.

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What do you expect from a postdoc experience?

If you’d like to tackle big questions in biology in one of the top inter-disciplinary research institutes in the world, you should apply for the Charles H. Best Postdoctoral Fellowship at the Donnelly Centre in Toronto.

At the state-of-the-art Donnelly Centre, our researchers always seek new ways to study gene regulation, signal transduction, development, systems biology, proteomics, computational biology and functional genomics.

Our ideal candidate is a highly qualified graduate (2 years or less postgraduate) in the field of molecular, genetic and genomic research. Send your application to one or two primary faculty members in the Donnelly Center (Andrews, Bader, Blencowe, Boone, Caudy, Emili, Fraser, Greenblatt, Hughes, Kim, Krause, Moffat, Morris, Roth, Ryu, Sidhu, Taipale, Zhang), whose interests match your own (www.thedonnellycentre.utoronto.ca). Once you’ve agreed sponsorship with a faculty member, you must then send them a curriculum vitae, one page statement of research interests, transcripts, and three letters of reference. The deadline for applications is September 25, 2015. We will support the successful applicant for up to two years with a generous stipend. For additional information please visit www.charlesbestfoundation.ca .

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This editorial by Ross Cagan was first published in Disease Models & Mechanisms.

I entered the science field because I imagined that scientists were society’s “professional risk takers”, that they like surfing out on the edge. I understood that a lot of science – perhaps even most science – has to be a solid exploration of partly understood phenomena. But any science that confronts a difficult problem has to start with risk. Most people are at least a bit suspicious of risk, and scientists such as myself are no exception. Recently, risk-taking has been under attack financially, but this Editorial is not about that. I am writing about the long view and the messages we send to our trainees. I am Senior Associate Dean of the graduate school at Mount Sinai and have had the privilege to discuss these issues with the next generation of scientists, for whom I care very deeply. Are we preparing you to embrace risk?

As a long-standing academic scientist, I like my tenure and my funding to arrive with minimum risk. Although this is a reasonable response to wanting a good life, it is not always the optimal approach for solving 21st-century biomedical problems. It discourages risk-taking and encourages playing to the grant agencies. Worst of all, my generation’s fear of risk bleeds down to you. We teach you how to design projects that are ‘bullet-proof’. You will build the Biomedicine Age, and you will need to take risks to do it.

A friend and serial entrepreneur once commented that “scientists can be quick to ‘go negative’…unusual ideas are met with ‘that won’t work’”. I would not go that far, but he does have a point. Most risky ideas don’t pan out and, if I just dismiss them, my batting average will be pretty high. But hard problems will never get solved, and some of the magic of science is lost. Try a lab meeting some time with a simple rule: no negative comments, only “yes, and…”. Perhaps the student’s idea is not exactly right but the really great idea is lurking nearby. Kill the first, and the great idea is also lost. This all feeds to a culture of innovation and risk.

Risk in the Biomedicine Age

Biomedical science today is in a similar position as the computer industry of the early 1980s. Then, computer research was dominated by government funding and made up mainly by academics, mostly physicists and mathematicians. The government decided that it was not going to increase funding and the computer industry was faced with a challenge. The next generation was all in: they believed they could make a difference, and they did. They opened their garages and built the Information Age. If you tell someone in Silicon Valley that a great project is risky, that’s considered a bonus.

We are now entering the Biomedicine Age. Our great challenge is to understand how our body works and bring that understanding to erasing disease. Cancer, heart disease, infection, neurodegenerative diseases and – perhaps our most profound health challenge – mental illness all represent hard problems that will transform who we are when they are solved. The key words here are ‘risk’ and ‘diversity’ (more on diversity in a future Editorial). Biomedical challenges will require biology PhD’s entering basic research as explorers, industrial research to create therapeutics, Wall Street to build its financial underpinnings, and professional communicators to explain it all to society. The brains-in-the-garage are…you.

This will require loving risk. Start a company. It will probably fail (mine did), but then start another (working on that). Worried that funding for startups is tight, that you will confront the ‘valley of death’? There is a much better financial structure now in biomedicine than there was for computers 30 years ago. We need your creativity. Apps, small devices, computational algorithms, blogs, new materials, innovative teaching etc. are all part of the Biomedicine Age. Create a new way of thinking about old problems and find a way to make your solution happen. Then find someone who will mentor you, encourage you that your idea is actually great. Succeeding will be sweet.

(3 votes)

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This cartoon was first published in the Journal of Cell Science. Read other articles and cartoons of Mole & Friends here.

Part I- ‘The imposter’

Part II- ‘The teaching monster’

Part III- ‘The Pact’

(2 votes)

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The laboratory mouse has been a popular model in mammalian biology for obvious reasons and it has contributed to a number of landmark discoveries in biomedical research. Despite this, few courses and summer schools – which train future leaders in this field – focus on mouse genetics. Phenomin, a large-scale French national infrastructure for biology and health has organised the first European Advanced School for Mouse Phenogenomics. I was fortunate to be selected to participate in this school, which was held last month at a French château set atop a picturesque Alsacian landscape, some 30 miles from Strasbourg.

The theme of the school was “good practices regarding the use of mouse models for biomedical research”. The four-day programme encompassed topics on mouse genetics, mutagenesis, functional tests using mouse models and international initiatives, databases and resources. Around 30 experts from these areas engaged the participants with their various talks and discussions.

Participants were mostly PhD students and some postdocs. The school began with a talk by Dr Yann Hérault of the Mouse Clinical Institute (ICS), Strasbourg. He introduced the structure and goals of Phenomin. Following this, Professor Emeritus Jean-Louis Guénet of Institut Pasteur gave an excellent lecture on the different populations of laboratory animals. He took us through the classical aspects of mouse genetics that reminded us of our university genetics lessons and refreshed our knowledge of this topic. This talk served as a prelude to the other sessions.

Many talks focused on recent advances in mutagenesis methods, especially the CRISPR/Cas9 technology. Although this method has been developed only recently, many labs around the world have picked it up quickly. One of the key advantages of this method is that it allows researchers to produce mouse mutants in a very short space of time, with fewer or no off-target effects when compared to other nuclease mediated mutagenesis methods. During the school, we discussed the limitations of this method, especially the ability to produce conditional/inducible mutants. As we speak, a paper published last week by the Zhang lab (MIT) shows inducible human stem cell lines (with the Flp/FRT and Cre/LoxP system) engineered by CRISPR/Cas9 method by dual guide RNA targeting. This method is becoming user-friendly, favourable and a key addition to the existing mouse genetics tool box. During my short early academic career, I have witnessed at least four different mutagenesis methods; some of them disappeared and some have become famous. Without doubt, mouse genetics will see more new technologies appearing in the future that will hugely influence our current understanding of many aspects of mouse biology. It is very exciting to be a researcher in this era of cutting-edge molecular technologies.

There was also a focus on the large-scale resources and data that are available for the mouse genetics community, especially on those generated for knockout mice via international efforts. My PhD work itself was carried out within a close collaboration with such a consortium. Although these resources have been available for many years, I often come across young researchers who weren’t aware of these valuable sources of mouse mutants. International efforts to build such resources allow researchers to save time on producing mutants and spend more time on the research question itself. The IKMC (International Knockout Consortium) is aimed at generating and distributing mouse mutants for each and every gene in the mouse genome. The IKMC has now spun out as IMPC (International Mouse Phenotyping Consortium), which phenotypes the mutants that are produced through IKMC and makes open access of the data. Gone are the days when a PhD student or a postdoc spent their entire time on generating a knockout mouse. Now they can just ‘stop-and-shop’ a desired mutant and start the experiment without spending much time on the generating the mutant itself. The open access data on primary phenotype from IMPC could be exploited to build hypotheses and test them. Also, there exists a resource database, CREATE (Coordination of resources for conditional expression of mutated mouse alleles) for Cre driver lines for those who are interested in conditionally ablating the genes in their desired cell types – the cherry on top of the cake!

The other topic I found very interesting was immunophenomics. Professors Bernard Malissen and Marie Malissen gave insights into pilot scale immune phenotyping studies to elucidate immune complexity through functional genomics. Professor Bernard Malissen runs an ambitious project at CIPHE, the centre for Immunophenomics at Marseille-Luminy where they aim to phenotype all the cellular components of the immune system under steady state and when challenged with pathogens. The outcome of their research holds great promise in the field of immunology and infection biology.

Ethics and animal welfare were discussed intensely during the school. The participants were reminded how to consider ethics and welfare of the animal throughout their research. Dr Jan-Bas Prins of LUMC, Netherlands gave an eye-opening lecture on ethics and humane animal research. He stressed how researchers should keep in mind the principles of 3-Rs (replacement, reduction, and refinement) throughout their animal experiments.

The highlight of the school’s programme was the workgroup sessions, where the participant groups were given topics (outside their own research) and relevant articles to discuss. They were also assigned to a supervisor/expert with whom they could discuss the topic and finally present it for a general discussion. This allowed the participants to critically go through the assigned topic and brainstorm the questions addressed and mouse techniques used in the studies. In my case at least, I gained ‘enlightenment’ on T-cell receptors – the topic which was assigned to my group and something which was totally new to me! The school also saw two poster sessions with PhD students and postdocs showcasing their excellent works involving various mouse mutants and their relevance to various diseases.

Kudos to the organisers of the school! They did a fantastic job of putting together a programme which perfectly fitted the needs of mouse genetics researchers and those who have begun their PhD studies. I hope the organisers will be able to secure funding to conduct the school in coming years. Although the sun decided not to shine during most of the days of the school, we were intensely soaked with science throughout the week!

This post is also available from our lab blog – wattlab blog. Please visit for more interesting topics and discussions.

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Here are the highlights from the current issue of Development:

HIF1α muscles in on regeneration

During early development, skeletal muscle stem/progenitor cells (SMSPCs) are thought to reside in low O₂ levels but how this hypoxic environment affects myogenesis in vivo is unclear. Here, Celeste Simon and colleagues investigate the role of hypoxia inducible factor 1α (HIF1α), which mediates the cellular sensing of O₂, during skeletal muscle development and regeneration in mice (p. 2405). They first show that HIF1α is in fact dispensable for embryonic and fetal myogenesis; the inactivation of Hif1a in PAX3-expressing SMSPCs does not affect progenitor cell homeostasis or the formation of embryonic and fetal muscles. In contrast, they report, the deletion of Hif1a in PAX7-expressing progenitors in adult mice accelerates muscle regeneration after ischemic injury, suggesting that HIF1α normally acts to impede muscle regeneration. The researchers further demonstrate that HIF1α represses the canonical Wnt signalling pathway, which is known to promote muscle regeneration after injury. Together, these findings confirm that the HIF pathway regulates myogenesis in vivo and reveal a novel link between O₂ sensing and Wnt signalling during development and regeneration.

Top Notch insights into differential signalling

The two closely related mammalian Notch receptors Notch1 and Notch2 have been shown to play different, and sometimes opposing, roles in development and disease. But what is the mechanistic basis of these differences? Here, Raphael Kopan and colleagues address this question using mice in which the intracellular domains (ICDs) of these two Notch receptors have been swapped (p. 2452). They first show that ICD swapping has little effect on the development of organs in which either Notch1 (T cells, skin, the inner ear and endocardium) or Notch2 (the liver, eye, cardiac neural crest and lung) is known to act alone or is dominant over it paralogue, suggesting that the ICDs are interchangeable. In the case of Notch dosage-sensitive tissues, the researchers further show that the phenotypes observed are due to haploinsufficiency and not due to ICD composition. Together, these and other findings lead the authors to conclude that both the strength of Notch signalling (defined by the number of ICD molecules that get cleaved from the receptor and reach the nucleus) and the duration of signalling (the half-life of active ICD complexes) contribute to the differences between Notch1 and Notch2 functions in many developmental contexts.

An extended view of musculoskeletal development

The musculoskeletal system is made up of a number of tissue types, including bone, muscle, tendon and cartilage. While the development of each of these tissues has been studied, how they integrate into a functional superstructure, and the extent to which they develop independently, is unclear. Now, Ronen Schweitzer and co-workers investigate this interdependency by analysing tendon development in mice that have defective muscle or cartilage developmental programmes (p. 2431). They report that whereas tendon development in the zeugopod (arm/leg) is dependent on muscle, autopod (paw) tendon development occurs independently of muscle and instead requires cues from skeletal tissues. These findings suggest that autopod and zeugopod tendon segments can develop independently and, in line with this, the researchers demonstrate that they are derived from distinct progenitor pools. They further show that tendons are integrated in a modular fashion, whereby zeugopod muscles first connect to their respective autopod tendon via an anlagen of tendon progenitors in the presumptive wrist and the tendons then elongate proximally in parallel with skeletal growth. Based on their findings, the authors put forward a novel integrated model for limb tendon development.

Fishing for clues into tooth replacement

Unlike mice and humans, basal vertebrates such as sharks and fish exhibit continuous tooth renewal and thus offer an attractive model for studying tooth replacement. Here, by taking advantage of the natural variation in threespine stickleback fish populations, Craig Miller and colleagues examine the genetic and developmental basis of tooth regeneration (p. 2442). They first compare the tooth morphology of three laboratory-reared populations: one marine population and two freshwater populations. They report that, relative to the ancestral marine population, the two freshwater populations exhibit increased numbers of pharyngeal teeth, increased tooth plate areas and decreased intertooth spacing. The increase in tooth number, they demonstrate, occurs late in development and is due to an elevated rate of tooth replacement. When comparing the two freshwater populations, the researchers further note that the spatial patterning of newly formed teeth and the timing of their emergence differ between the two populations, suggesting that they use distinct developmental mechanisms. Finally, using quantitative trait loci mapping, the researchers show that different genomic regions contribute to the increase in tooth number in the two freshwater populations. These findings support a model for convergent evolution via distinct developmental routes and provide insights into the genetic factors that govern tooth replacement.

PLUS:

An interview with Brigid Hogan

We recently interviewed Brigid Hogan, a developmental biologist who has worked extensively on the early stages of mouse development and is now unravelling the mysteries of lung organogenesis. She is the George Barth Geller Professor and Chair of the Department of Cell Biology at Duke University Medical Center. Brigid is also the winner of the 2015 Society for Developmental Biology (SDB) Lifetime Achievement Award. See the Spotlight article on p. 2389

The retromer complex in development and disease

The retromer complex is a multimeric protein complex involved in recycling proteins from endosomes to the trans-Golgi network or plasma membrane. Here, Wang and Bellen summarise the role of the retromer complex in developmental processes, neuronal maintenance, and human neurodegenerative diseases. See the Development at a Glance article on p. 2392

LIN28: roles and regulation in development and beyond

LIN28 is an RNA-binding protein best known for its roles in promoting pluripotency via regulation of the microRNA let-7. However, recent studies have uncovered new roles for LIN28, suggesting that it is more than just a regulator of miRNA biogenesis. Here, Tsialikas and Romer-Seibert review how LIN28 functions in development and disease. See the Primer on p. 2397

(1 votes)

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The 4th meeting in the Abcam Adult Neurogenesis conference series was held in the beautiful city of Dresden earlier this year. The conference’s aim was to put the developmental process of adult neurogenesis and its regulation into the wider context of its functional and presumed evolutionary relevance.

Reporting from the meeting was our roving reporter, Nambirajan Govindarajan (winner of The Node and Abcam’s joint Meeting Reporter competition). He tweeted his way through the meeting and has written an insightful report of this meeting. Thanks Govind!

Adult Neurogenesis at 50: the Dresden chronicles

This year marks the 50^th anniversary of the first publication showing adult neurogenesis in mammals (Altman and Das, 1965). The growth and development of this field was commemorated by the Abcam conference on Adult Neurogenesis: Evolution, Regulation and Function in May this year in the beautiful baroque city of Dresden.

All good tales start with “Once upon a time,” and this was no exception. Gerd Kempermann kickstarted the meeting with his enchanting narrative on the serendipitous birth of the field and its ebbs and flows over the past five decades. While studying neuronal activity in the adult rat brain, Joseph Altman switched from tritiated leucine to the more sensitive tritiated thymidine to calibrate his detection and accidentally observed proliferating cells in the rat hippocampus. He published his findings with Gopal Das in a seminal paper, which gave birth to the ‘science of the future’ that would change Santiago Ramón y Cajal’s harsh decree (Ramón y Cajal, 1928; Altman and Das, 1965). This chance discovery has spawned a long line of research on adult neurogenesis in many avian, piscine and mammalian species. Kempermann recounted various contrasts and conflicts among the research and researchers in the field and even dispelled some outstanding myths. He emphasised the role of adult neurogenesis in mediating brain plasticity, which correlates with neural complexity along the evolutionary tree. Being the expert raconteur, Kempermann delighted us all and set the stage for the meeting.

Open questions in adult neurogenesis

The eminent Fred Gage laid forth the big questions facing adult neurogenesis in his keynote lecture. He focused on the role of the niche in regulating neurogenesis. How different are the two known neurogenic zones – the subventricular zone (SVZ) and the dentate gyrus (DG)? How are the precursors affected by the niche vasculature and metabolic state? Taking it a step further, Gage even wondered if a cell isolated from a non-neurogenic area would become neurogenic if transplanted into either niche. Tackling these questions is essential in understanding the function, regulation and evolution of adult neurogenesis. Gage also remarked that other potential niches such as the striatum, angular gyrus, cortex and spinal cord need to be investigated. He then reminded us of the standing questions in the field – the precise molecular nature of different neurogenic cell types and the comparability of the in vitro and in vivo scenarios. It is also unclear how the number of divisions of a precursor cell is regulated. Gage also emphasised the need to understand the integration of newborn neurons in the neural network and whether cellular excitability and network activity influence this process. Another heavily debated issue is whether and how adult neurogenesis contributes to cognition. The mechanisms that modulate environmental regulation of adult neurogenesis are still unknown. These are all open questions that Gage urged us to pursue and discuss. Finally, anticipating the biggest question on everyone’s mind, Gage also brought up the role of adult neurogenesis in ageing and neurological disease. Can restoring adult neurogenesis help a degenerating brain? These open questions promise to fuel neurogenesis research further and hopefully unravel the intricate codes governing this enigmatic part of us we call our brain.

Born in the wild

Neurons are born in the wild too! To enrich laboratory research with some wild data, this meeting brought together some species very different from inbred rodents – mole-rats, silver foxes, dolphins and warblers. Irmgard Amrein introduced a technical issue that we lab folks take for granted. How does one assess a wild animal’s age? Amrein has used parameters such as teeth wear, lens weight and bone maturation to closely estimate age in the wild. Her group has found that adult neurogenesis is lower in subterranean rodent species compared to terrestrial ones (Amrein et al., 2014). According to Amrein, lower habitat demand on subterranean species correlates with lower adult hippocampal neurogenesis (AHN). She then moved on to the effect of domestication and social interaction on AHN in wild and farm-bred silves foxes at Dimitri K. Belyaev’s unique fox farm in Novosibirsk. Belyaev has selectively bred silver foxes (Vulpes vulpes) based on their tameness, which he believes is how they were originally domesticated (Belyaev, 1979). These domesticated foxes selected for their tameness showed higher hippocampal cell proliferation and neuronal differentiation compared to unselected controls (Huang et al., 2015). These findings suggest that AHN might be involved in interspecific social interaction. We then dived into the cetaecean brain with Paul Manger who vivdly illustrated that dolphins lack AHN, which correlates with their aquatic habitat, lack of olfaction underwater and early-life insomnia. Even as grown-ups, dolphins sleep without any REM phase and possess a small, rudimentary DG with almost no AHN (Patzke et al., 2015). We need to test this interesting hypothesis in other sleepless species before firmly establishing a link. Manger also found that doublecortin immunoreactivity rapidly decreased with post-mortem delay and thus rendered the ex vivo analysis of neuronal differentiation in wild species extremely challenging. From the oceans Anat Barnea took us flying with her migrant reed warbler (Acrocephalus scirpaceous) that recruits more new neurons than the resident, closely-related Clamorous warbler (A. stentoreus) (Barkan et al., 2014). Barnea’s findings support the role of adult neurogenesis in spatial navigation and adaptation to changing environments. Altogether, the ‘wild’ talks gave us an insight into how adult neurogenesis could have evolved and how it affects the behaviour of animals in their natural habitat.

Studied in the lab

We moved from the wilderness to the laboratory. Wieland Huttner touched upon the evolutionary expansion of the human neocortex, which results from embryonic basal progenitor cell proliferation in the SVZ. Huttner presented the role of ARHGAP11B, a gene that was partially duplicated after the human evolutionary lineage split from the chimpanzee. This gene promotes basal progenitor generation and proliferation in mice, can induce folding of the developing mouse neocortex, and might have contributed to the expansion of the human neocortex (Florio et al., 2015). We delved deeper into the molecular mechanisms regulating neurogenesis. Federico Calegari presented his unique approach combining DNA adenine methyltransferase identification (DamID) with deep sequencing to discover the function of novel genes involved in corticogenesis (Aprea et al., 2013). His group has characterised Tox, a novel switch gene that regulates cortical development in mice (Artegiani et al., 2015). Stephan Schwarzacher discussed the integration of newborn neurons. By studying the activation of immediate early genes including c-Fos, Arc and Zif after high-frequency stimulation, Schwarzacher has concluded that full functional integration of newborn neurons follows and closely correlates with their structural maturation (Jungenitz et al., 2014). Juan M. Encinas has stimulated the hippocampus with kainic acid (KA) and observed that seizures induced neural stem cells (NSCs) to form reactive astrocytes whereas subthreshold excitation activated the NSCs and eventually triggered them to form astrocytes. In both cases, Encinas found that KA impaired neurogenesis in the long term (Sierra et al., 2015). Live imaging of newborn neurons in vivo is one of the technological breakthroughs of the 21^st century. Fred Gage and Sebastian Jessberger both presented this approach to investigate AHN and dendritic morphology of newborn neurons. Jessberger impressed us with the depth of imaging achieved, using a cranial window preparation that leaves the hippocampal formation intact, including the CA1. Hongjun Song presented his findings on distinct radial glia-like stem cell populations, labelled by specific markers such as Nestin, Gli and Mash, and discussed their properties. Song’s pioneering work on single-cell analysis of adult neurogenesis is sure to pave the way in analysing specific cell populations and unravelling the cellular heterogeneity in the neurogenic niches.

Learning what they do

Studying the evolution and regulation of adult neurogenesis leads us to the most intriguing question: how is adult neurogenesis involved in brain function? Paul Frankland refreshed our memory of the role of AHN in forgetting. According to Frankland, upregulating AHN by running induces forgetting in mice (Akers et al., 2014). Interestingly, Frankland has found that during reversal learning in the water maze, mice seem to learn the new location of the platform better with more new neurons in their hippocampi. But does that mean they have forgotten where the platform was previously placed? Frankland’s findings sparked an exciting discussion on the nature of memory and how the brain actually forgets a memory. Spatial learning was further discussed by Nora Abrous whose recent work suggests that water maze learning does not affect cell proliferation or survival in the adult mouse DG (Trinchero et al., 2015). Benedikt Berninger discussed a different angle on the role of experience in regulating adult neurogenesis. Berninger reported that environmental enrichment within a critical window of 2-6 weeks after the birth of new neurons significantly modulates their development and integration (Bergami et al., 2015).

The relation between AHN and stress was keenly discussed at the meeting. Carlos Fitzsimons ‘stressed’ that glucocorticoids regulate stress-induced adult neurogenesis through epigenetic mechanisms. Corticosterone treatment transiently reduced proliferation by modulating DNA methylation. Could this modulate the inheritance of stress effects? Recent work by Fitzsimons demonstrates that the glucocorticoid receptor regulates the maturation and integration of newborn neurons and plays an important role in contextual fear conditioning (Fitzsimons et al., 2013). Another interesting talk along these lines by Yassemi Koutmani discussed the role of corticotrophin-releasing hormone (CRH) in upregulating AHN thereby reversing the damage by glucocorticoid treatment. Koutmani’s work depicts that CRHR1 is critically involved in regulating how NSCs respond to environmental stimuli (Koutmani et al., 2013). Friederike Klempin presented her findings on the role of ACE2 activity that sustains brain serotonin level, which in turn mediates the fast neurogenic response of the niche to physical activity (Klempin et al., 2013).

When it comes to regenerating the brain, the zebrafish swims miles ahead of mammals. Caghan Kizil has generated a zebrafish model for chronic neurodegeneration by injecting Aß42 peptides into their brain, which leads to cell death, inflammation, synaptic degeneration and memory impairment. However, Kizil found that unlike in mammals, Aß42 treatment triggered stem cells in the zebrafish brain to proliferate and remarkably form new neurons. Such studies on neuroregeneration in the fish can be extremely valuable in designing new therapies against neurodegeneration.

Concluding remarks

Half a century bygone and adult neurogenesis has evolved into a mainstream research discipline in neurobiology. It was born by chance, differentiated into a distinct lineage, carved out its own niche, migrated all over the world and has integrated perfectly within the extensive network of biomedical science, mirroring the life of the very cells it studies. Many questions have been answered and many more daunt us still. With further technical innnovations, better models and cross-species experiments, the coming decades are bound to keep us busy uncovering the secrets of how and why our brains make new neurons lifelong.

References

Akers, K. G., Martinez-Canabal, A., Restivo, L., Yiu, A. P., De Cristofaro, A., Hsiang, H. L., Wheeler, A. L., Guskjolen, A., Niibori, Y., Shoji, H. et al. (2014) ‘Hippocampal neurogenesis regulates forgetting during adulthood and infancy’, Science 344(6184): 598-602.

Altman, J. and Das, G. D. (1965) ‘Post-natal origin of microneurones in the rat brain’, Nature 207(5000): 953-6.

Amrein, I., Becker, A. S., Engler, S., Huang, S. H., Muller, J., Slomianka, L. and Oosthuizen, M. K. (2014) ‘Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species’, Frontiers in neuroanatomy 8: 39.

Aprea, J., Prenninger, S., Dori, M., Ghosh, T., Monasor, L. S., Wessendorf, E., Zocher, S., Massalini, S., Alexopoulou, D., Lesche, M. et al. (2013) ‘Transcriptome sequencing during mouse brain development identifies long non-coding RNAs functionally involved in neurogenic commitment’, The EMBO journal 32(24): 3145-60.

Artegiani, B., de Jesus Domingues, A. M., Bragado Alonso, S., Brandl, E., Massalini, S., Dahl, A. and Calegari, F. (2015) ‘Tox: a multifunctional transcription factor and novel regulator of mammalian corticogenesis’, The EMBO journal 34(7): 896-910.

Barkan, S., Yom-Tov, Y. and Barnea, A. (2014) ‘A possible relation between new neuronal recruitment and migratory behavior in Acrocephalus warblers’, Developmental neurobiology 74(12): 1194-209.

Belyaev, D. K. (1979) ‘The Wilhelmine E. Key 1978 invitational lecture. Destabilizing selection as a factor in domestication’, The Journal of heredity 70(5): 301-8.

Bergami, M., Masserdotti, G., Temprana, S. G., Motori, E., Eriksson, T. M., Gobel, J., Yang, S. M., Conzelmann, K. K., Schinder, A. F., Gotz, M. et al. (2015) ‘A critical period for experience-dependent remodeling of adult-born neuron connectivity’, Neuron 85(4): 710-7.

Fitzsimons, C. P., van Hooijdonk, L. W., Schouten, M., Zalachoras, I., Brinks, V., Zheng, T., Schouten, T. G., Saaltink, D. J., Dijkmans, T., Steindler, D. A. et al. (2013) ‘Knockdown of the glucocorticoid receptor alters functional integration of newborn neurons in the adult hippocampus and impairs fear-motivated behavior’, Molecular psychiatry 18(9): 993-1005.

Florio, M., Albert, M., Taverna, E., Namba, T., Brandl, H., Lewitus, E., Haffner, C., Sykes, A., Wong, F. K., Peters, J. et al. (2015) ‘Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion’, Science 347(6229): 1465-70.

Huang, S., Slomianka, L., Farmer, A. J., Kharlamova, A. V., Gulevich, R. G., Herbeck, Y. E., Trut, L. N., Wolfer, D. P. and Amrein, I. (2015) ‘Selection for tameness, a key behavioral trait of domestication, increases adult hippocampal neurogenesis in foxes’, Hippocampus.

Jungenitz, T., Radic, T., Jedlicka, P. and Schwarzacher, S. W. (2014) ‘High-frequency stimulation induces gradual immediate early gene expression in maturing adult-generated hippocampal granule cells’, Cerebral cortex 24(7): 1845-57.

Klempin, F., Beis, D., Mosienko, V., Kempermann, G., Bader, M. and Alenina, N. (2013) ‘Serotonin is required for exercise-induced adult hippocampal neurogenesis’, The Journal of neuroscience : the official journal of the Society for Neuroscience 33(19): 8270-5.

Koutmani, Y., Politis, P. K., Elkouris, M., Agrogiannis, G., Kemerli, M., Patsouris, E., Remboutsika, E. and Karalis, K. P. (2013) ‘Corticotropin-releasing hormone exerts direct effects on neuronal progenitor cells: implications for neuroprotection’, Molecular psychiatry 18(3): 300-7.

Patzke, N., Spocter, M. A., Karlsson, K. A. E., Bertelsen, M. F., Haagensen, M., Chawana, R., Streicher, S., Kaswera, C., Gilissen, E., Alagaili, A. N. et al. (2015) ‘In contrast to many other mammals, cetaceans have relatively small hippocampi that appear to lack adult neurogenesis’, Brain structure & function 220(1): 361-83.

Ramón y Cajal, S. (1928) Degeneration and Regeneration of the Nervous System: Oxford Univ. Press, London.

Sierra, A., Martin-Suarez, S., Valcarcel-Martin, R., Pascual-Brazo, J., Aelvoet, S. A., Abiega, O., Deudero, J. J., Brewster, A. L., Bernales, I., Anderson, A. E. et al. (2015) ‘Neuronal hyperactivity accelerates depletion of neural stem cells and impairs hippocampal neurogenesis’, Cell stem cell 16(5): 488-503.

Trinchero, M. F., Koehl, M., Bechakra, M., Delage, P., Charrier, V., Grosjean, N., Ladeveze, E., Schinder, A. F. and Abrous, D. N. (2015) ‘Effects of spaced learning in the water maze on development of dentate granule cells generated in adult mice’, Hippocampus.

(4 votes)

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Salary: £28,695-£37,394

Reference: PS06656

Closing date: 31 August 2015

We are looking for three motivated, ambitious and independent post-doctoral researchers to join an interdisciplinary research project on Alzheimer’s disease, developing novel models of human white matter, single-molecule fluorescence techniques, sensitive biosensors and cutting-edge optical imaging methods. The project is ambitious, aiming to make step changes in human stem cell development, tissue culture engineering, biosensor generation and understanding of Alzheimer’s disease.

This focused collaborative project brings together the expertise of:

Dr. Káradóttir (Wellcome Trust – MRC Stem Cell Institute: http://www.stemcells.cam.ac.uk/researchers/principal-investigators/dr-ragnhildur-thra-kradttir),

Dr. Lee (Dept. of Chemistry: http://www.ch.cam.ac.uk/person/sl591),

Prof. Spillantini (Dept. of Clinical Neuroscience: http://www.brc.cam.ac.uk/principal-investigators/maria-spillantini/),

Dr. Coleman (John van Geest Centre for Brain Repair: http://www.neuroscience.cam.ac.uk/directory/profile.php?mcoleman),

Prof. Brayne (Institute of Public Health: http://www.iph.cam.ac.uk/about-us/key-people/carol-brayne/),

Prof. Brown (Dept. of Biochemistry: http://www.bioc.cam.ac.uk/people/uto/brown),

and Prof. Hall (Dept. Chemical Engineering and Biotechnology: http://www.ceb.cam.ac.uk/directory/lisa-hall), all based at the University of Cambridge.

This multi-departmental arrangement provides an excellent environment for research and career development, as the post holders will benefit from the resources and expertise of biological, physical and medical sciences in this multidisciplinary project.

Requirements:

We are looking for candidates that hold a PhD, (1) in the field of neuroscience/biochemistry/stem cell biology/medicine, and (2) candidates which hold a PhD in the field of chemistry/bioengineering/engineering/biophysics. Candidates with experience in cross-disciplinary research are particularly encouraged to apply.

The successful candidates will have a strong publication record and enjoy ambitious projects at the frontiers of neuroscience and biotechnology. We are specially looking for candidates that are self-motivated, collaborative with effective communication skills and enjoy working in a team. Proven capacity to design, execute, and interpret experimental data is essential.

Applicants should have obtained (or expect to obtain) one of the following:

(1) a PhD in neuroscience/biochemistry/stem cell biology/medicine. Experience in tissue culture methods (such as deriving neuronal cells from human IPSCs), fluorescence imaging or neurodegenerative disease, is highly advantageous.

(2) a PhD in biophysics, physical chemistry, photonics, optics or related disciplines. Experience with single-molecule fluorescence techniques, generation of biosensors or electrochemical engineering would be highly advantageous. Candidates should have a keen interest in applying physical methods to complex biological systems, although no prior knowledge of neurodegenerative disease or biology is required, and enjoy working in a highly multidisciplinary environment.

(3) a PhD in either physical or life sciences, with a solid background in cross-disciplinary research, particularly in neuroscience and biophysics or bioengineering. Experience with fluorescence techniques, generation of biosensors or electrochemical engineering, electrophysiology, or tissue culture methods/engineering development, would be highly advantageous.

Start date is flexible but can be as early as October 2015.

Fixed-term: The funds for this post are available until 30 September 2018 in the first instance.

To apply online for this vacancy and to view further information about the role, please visit: http://www.jobs.cam.ac.uk/job/7634. This will take you to the role on the University’s Job Opportunities pages. There you will need to click on the ‘Apply online’ button and register an account with the University’s Web Recruitment System (if you have not already) and log in before completing the online application form.

The closing date for all applications is Monday 31 August 2015.

Please upload your Curriculum Vitae (CV) and a covering letter in the Upload section of the online application to supplement your application. If you upload any additional documents which have not been requested, we will not be able to consider these as part of your application.

Informal enquiries about the post are also welcome via email on jobs@stemcells.cam.ac.uk.

Interviews will be held in mid-September 2015. If you have not been invited for interview by 15 September 2015, you have not been successful on this occasion.

Please quote reference PS06656 on your application and in any correspondence about this vacancy.

The University values diversity and is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

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Last week, the SDB hosted what may well have been its highest annual meeting – at 8000 feet – in Snowbird, Utah. The atmosphere was fantastic, the talks were phenomenal, and the scenery was just obscene. It was an all-around great meeting, topped with a choir of singing PIs after the conference dinner. Couldn’t get better. If you missed it you can always catch up with what happened at #2015SDB.

On Sunday, Mary Dickinson moderated a workshop on imaging and quantitative biology where we realized many of us are faced with a number of common issues we are yet to resolve. A very useful discussion ensued with some ideas on how to solve them, so I thought it would be good to continue that conversation here where anyone interested can share information, ideas and resources. I would like it to be an open forum for anyone to contribute questions, and solutions and also to correct inaccuracies and dispel misconceptions. I will keep the post updated with a summary of suggestions and any consensus we might reach, so stay tuned…

Two of the problems raised at the SDB workshop had to do with
(1) quantification of fluorescence in whole-mount images and
(2) data sharing and public access.

Fluorescence quantitation really is a combination of several problems, since many variables can affect the resulting image: from sample fixation to antibody performance and acquisition parameters (if dealing with fixed specimens), and many others. For these and other reasons, many take fluorescence quantitation with a grain of salt. Nonetheless, if done carefully some of us believe it can be very informative. On the other hand, data gathered from fluorescent reporters (such as GFP or GFP fusions) is not affected by antibody, or other sample processing-related factors, and should therefore be much more straight forward to analyze. I do hope the experts will weigh in on some of these issues in the comments section. For instance: to what extent the use of photomultipliers (PMTs) in some confocal microscopes can undermine the results? Is there a reliable way to calibrate the microscopes prior to each imaging session in order to obtain comparable results?

For now, I just want to discuss one specific issue we, in the Hadjantonakis lab, have been trying to get around for some time: the intensity decay along the Z-axis, or Z-associated fluorescence decay (#callitwhatyouwant) in confocal images. When taking optical sections along the Z-axis in a confocal microscope, the further away from the lens the slice is, the dimmer the signal becomes (see Figure 1A, B). This is mainly due to the distance from the objective and the scattering of light through the sample. This is not a problem for image presentation; however, when comparing intensity between cell types, the differences due to cell position can be larger than real differences in expression, thus complicating the analysis.

# Fit a linear model (lm) to the corresponding fluorescence channel over Z
>lm(log(channel)~Z, data = dataframe)

# Output will yield two coefficients
# (Intercept)   Z 
# 5.23416     -0.02233

# Plot corrected values (requires ggplot2 package)
>qplot(Z, log(channel)+Z*0.02233, data = dataframe)

Figure 1. Fluorescence decay along the Z-axis. (A) Example of 4 days old mouse embryo with nuclei labeled with Hoechst and outer cells labeled with an AlexaFluor 488 secondary antibody. (B) Plots of the logarithm of Hoechst and AF488 values over Z for many embryos like the one shown in (A). (C) Same data as in (B), after correction of each value.

Another issue raised was that of data sharing and public access to raw data post-publication. While genomic data is made available on public repositories, imaging data is not routinely so. With increasingly large datasets being generated from image quantitation, we need to make them – and the code used for analysis – publicly available alongside the article. This is important for reproducibility of the data, to avoid the file drawer problem and for other groups to possibly address new questions. Moreover, for many of us novices, having your code and analysis made available is not only good from a transparency standpoint, but also may earn you feedback from others on how to improve it.

We therefore discussed about (a) where to store the data and (b) potential standards to share image metadata, acquisition parameters, etc. Regarding repositories, Katherine Brown, from Development, suggested Dryad and Figshare. While Dryad seems to be preferred by publishers, Figshare also allows the sharing of unpublished (and perhaps unpublishable) data. Both services allow permanent storage of large volumes of data that can be continuously updated and facilitate citations by providing a DOI. Code may be stored in standard Git repositories such as GitHub.

Whereas there may not be a single storage solution for everybody, it would be important to set some standards for the presentation and organization of data and metadata. Someone at the workshop even suggested a standardized file nomenclature. Metadata is often stored in the microscope file (but not always in TIFFs), so sharing the raw images would address that problem. I personally find it useful to save experimental details and results in tables with consistent headers so that they can be melted or cross-referenced when needed. Sharing these could be one way to make experimental details available.

I think the take home message is that we will all benefit from discussing these issues and sharing ideas, and we may even reach a consensus on how to proceed while it is relatively early in the game. Therefore, do get involved, and please engage anyone who you think may have something to contribute to the discussion! I look forward to getting tips and ideas and perhaps some concrete solution on how to move forward!

UPDATE: I just realized Katherine recently wrote a post on this second issue, please feel free to comment on either!

(7 votes)

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