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Evolution of the Human Neocortex: How Unique Are We?

Posted by , on 28 October 2013

“Evolution of the Human Neocortex: How Unique Are We?” was the question asked at the Wiston House in West Sussex from 22-25 September 2013.  Although we were hardly the first to consider whether the human brain is something special, the ‘unique’ pileup of methodological approaches likely improved the dialogue on this topic. My own presentation sought to link cells, cortical areas, and behavior, and certainly the new information I acquired will contribute to this.  Here is a summary and reaction to some of the themes that arose from the meeting:

A DIVERSITY OF ANIMALS MODELS AND NEOCORTICAL STRUCTURES ARE LINKED BY THEIR SIMILARITIES. Zoltán Molnár stressed structural similarities between mammalian and bird cortex — but noted that these have been found despite of developmental differences. Tatsumi Hirata suggested that the mammalian neurogenic sequence, in which cortical layers result from stem cells each generating both deep and upper layer neurons, is primitive, and that isolated chick neurons developed in culture ‘revert’ to a similar developmental pattern. Luis Puelles found that, in mice, the claustrum arises very early in development, and insula cells migrate across it – confirming our neuroanatomist forefathers (Meynert, Brodmann, Cajal, Rose) who described claustrum as a deep layer of the insula in humans. To wrap things up, the continuity of brain function was addressed by Constance Scharff, who played a German folk tune sung beautifully… by a bullfinch.

GIVEN THESE REGULARITIES WHICH OVERREACH TAXONOMIC LINES, STRUCTURAL CONSTRAINTS LIKELY UNDERLIE THEM. Talks hinted that cortical organization follows a continuum along a caudal-rostral gradient. Barbara Finlay showed that across species, the same patterns emerge: there is a decrease in neuron density along a caudal-rostral axis, with the highest density in the occipital pole. Also along a caudal-rostral axis, the layer widths change, with an increase in the proportion of cortex that is comprised of upper layers versus lower layers. This gradient recapitulates primate evolutionary trends exemplified in humans: decreased neuron density, and upper layer expansion, and anteriorly-skewed brain enlargement. This organization forces forward the processing of information; with a bigger brain, there is even more information compression along the axis.  Ed Lein showed that along the cerebral cortex, and within cortical lamina, a caudal-rostral gradient is followed by gene expression profiles – perhaps providing the developmental and functional basis of the similar structural pattern.  Although in terms of its transcriptome the cerebral cortex is a largely homogeneous tissue, its most caudal aspect, the primary visual area, is most district in humans, whereas the primary somatosensory area is most distinct in mice.

SEVERAL SPEAKERS DISCUSSED MECHANISMS FOR MAKING NEOCORTEX BIGGER AND MORE HUMAN. Arnold Kriegstein told that humans – compared to mice – have an enormous outer subventricular zone with fast-jumping radial glia. This mechanism shortens migration distance, and may be important for big brains. Svante Pääbo awed by extracting entire genomes from a Neanderthal and tiny bit of a Denisovan, and these archaic forms are identical to modern humans in genes relevant to language. Further hints at the role of FOXP2 in advanced cognition came from humanized mice which showed faster learning and minds surpass those of cave men; Not to mention Neanderthals wore makeup, Denisovans crossed oceans, and both contributed to modern human genomes! Franck Polleux presented that, uniquely in humans, there is a partial duplication of the gene SARGAP2. Structurally it plays a role in the higher dendritic spine density of human versus macaque interneurons; functionally this gene is associated with social cognition and object recognition. Gavin Clowry found evidence for greater connectivity in the GABAergic interneurons of human versus mouse cortex. Thus, human uniqueness has elements at the level of genes and neuron connectivity.

BRAIN REGIONS ARE COMPRISED OF NEURONS WHICH TOGETHER MAP THE BODY.  Jon Kaas gave the sole talk on brain area function, showing that primate posterior parietal cortex is subdivided according to specific ethnologically relevant motor functions (a pattern replicated in frontal lobe) but do not have distinct boundaries based on somatotopic maps. He told that in bigger brains, the addition of cortical areas could improve serial processing, as in a computer. Perhaps duplication of topographically defined areas has diversified brain functions in big-brained humans.  Barbara Finlay pointed out the importance of these incomplete areas for understanding how new areas arise.  Recent research suggests an emphasis on bottom-up processing during tool use in humans, which compared to chimpanzees have more parietal activity, and less prefrontal strain (Hecht et al 2013) perhaps resulting from duplicate cross-modal representations.  It would be curious to know the developmental mechanism for, and the function of, doubled posterior parietal representations which sometimes pop up in our species (e.g., Sereno and Huang 2006, subject 2).

HUMAN-SPECIFIC BRAIN REGIONALIZATION COULD EFFECT GYRIFICATION. Chris Walsh was informed by observations of a human pathology with reduced gyrification in Broca’s language area, due to a mutation in GPR56 noncoding sequence. Developmentally, expression of this gene seems to limit the sizes of the ventricular zone and outer subventricular zone, and also the thickness of the upper layers of the cerebral cortex. Dean Falk discussed differences in sulcal patterns between humans and apes, and provided new insights into what our most recent shared ancestor’s brain may have looked like, based on her description of the Sahelanthropus endocast. The little data extracted from fossil endocasts reveals that our brains are a bit different from those of the earliest members of the human lineage.

YET, UNFORTUNATELY, WE ARE STILL A LONG WAY FROM INTERPRETING BEHAVIOR FROM GYRI. Surprisingly, the mechanisms behind folding the cerebral cortex into gyri may be very primitive, and may not reflect functional networks. Talks by both Wieland Huttner and André Goffinet pointed to an early origin of gyrification in mammals, including data from converging models based in both phylogenetic and developmental studies. Victor Borell demonstrated a distinct gene expression pattern concurrent with the location of sulci in ferrets. This brought into question the classic tension based theory of gyrification (Van Essen 1997) described in Dean Falk’s talk, which was based on Colette Dehay and Pasko Rakic’s past work on striate and extrastriate cortex formation.

WHAT IS THE UNIT OF BRAIN ORGANIZATION ESSENTIAL FOR IDENTIFYING HUMAN UNIQUENESS? With variability in factors including genes, regulatory factors, proteins, cells, connections, timing, specificity, activity, structures, number, and size, there must have been near-infinite ways in which unique human cognitive capacities could have emerged! The victory of this meeting was in representing the diversity of levels of magnification, and how these interact, for there is no magical unit at only a single level.

OUR JOB NOW IS TO DRAW LINES AND RECONSTRUCT HISTORIES. Pasko Rakic illustrated this point in a cartoon: a mouse attempts to have cocktails with a human – but instead drops his glass. This humorously represents the investigation of genetic factors in human-specific limb development to gain historical insight into the evolution of our unique brains. However, I am also reminded that human uniqueness is the story of just one animal. I am astonished to consider the primitiveness of gyrification and neocortical lamination; and the convergence of singing. With the meteoric loss of the dinosaurs, whose brain and body sizes exceeded those of living birds, what unique behaviors might also have been lost?

If you are interested in topics like these I invite you to participate in ENBER, a network which brings together brain evolution researchers across the globe and across different fields.  ENBER includes a mailing list (@eurnetbrainevor) for sharing information about upcoming opportunities (meetings, grants, jobs, publications) and a researcher directory.  I also maintain a listing of brain evolution research results that have appeared in the news (@BrainEvolutionN), so please inform me if your research has recently received attention from the press.

More about this workshop:
Steve Briscoe discusses his impressions of the same meeting here.
Katherine Brown discusses a related public event here.

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BSDB Axon Guidance and Regeneration

Posted by , on 28 October 2013

This article was first published in the BSDB Summer newsletter
 

BSDB axon meeting Aberdeen1The Autumn Meeting of the BSDB on ‘Axon Guidance and Regeneration’, held on the  28th – 30th August, 2013 at the University of Aberdeen in the beautiful surroundings of Old Aberdeen, was an excellent conference of around sixty delegates, full of exciting talks, highly distinguished speakers, and many opportunities for interaction and fruitful discussion. Talks and posters throughout the conference ranged over a number of fascinating topics, including both classical and novel axon guidance mechanisms (how neurons project axons correctly to specific targets to achieve the circuitry of the nervous system) and how these findings may be used to promote axon regeneration after injury or disease. How different axons project to specific targets in the same environment was discussed in detail, including novel and exciting evidence to support the idea of how not only one specific axon guidance cue, but combined cues acting in synergy, combined with a variety of receptors on different cells, as well as translation and transcription, can guide axons.

We were extremely lucky to have two wonderful and inspiring plenary talks. Using the optic system as a model, Professor Carole Mason (Columia University, USA) showed her work on how a combination of the guidance molecules Sema6d, PlexinA1 and NRCAM are all required at the optic chiasm for contralateral retinal ganglion cell axons to cross the midline, an important mechanism for the correct connectivity of the visual system. These findings bring forward the idea that a consortia of guidance molecules and specification cues both on the axon growth cone and in the environment is needed for correct axon guidance. In addition, Professor Mason showed exciting new work on how the birthdate (neurogenesis rate) of different neurons in the eye may lead to specification of their identity. In the second plenary lecture, Professor Christine Holt (University of Cambridge, UK) showed us her fascinating work on how differential translation of the actin assembly machinery in different parts of the axon growth cone can lead to attraction or repulsion. This suggests that local translation in the axon, dendritic spine and surrounding cells can affect axon guidance and neuronal activity.

In addition, Paola Bovolenta (Instituto de Neurociencias, Spain) described her work on how different levels of the morphogen sonic hedgehog (Shh) in both RGC cells themselves and at the midline are important for correct guidance of RGC axons. Artur Kania (Institut de Recherches Cliniques De Montreal, Canada) and Franco Weth (Karlsruhe Institute of Technology, Germany) added to this theme and described complex and novel work showing how guidance cue additivity, synergy and a variety of forward/reverse and cis/trans signalling through multireceptor complexes on growth cones can guide axons.

How to study what happens to the circuitry of the nervous system when correct axon guidance is disturbed or incomplete was discussed by several speakers, in particular by using transgenic mouse, fish and fly models to disturb genes in particular parts of the optic system.

The function of nonneuronal cells in axon guidance and regeneration was also discussed. Iris Salecker (NIMR, UK) described how their beautiful imaging of CNS glia in Drosophila medulla neuropil glia (mng) mutants is helping to define the development of different glial classes and the nature of their association with developing axons, and to suggest novel genes involved in these processes. Charles ffrench-Constant (MRC Centre for Regenerative Medicine, UK) told us about his group’s work on oligodendrocytes and central remyelination, and in particular, how a limited window for CNS remyelination in the CNS by oligodendrocytes may be extremely important for targeting therapies in multiple sclerosis. Several talks focused on the genes and mechanisms controlling the physical process of axon extension and how these may be manipulated to promote axon regeneration. Kristjan Franze (University of Cambridge, UK) used high-resolution ‘stiffness’ maps of Xenopus brain tissue to show that axonal growth speed and length is affected by the ‘stiffness’ of the axonal growth substrate. This exciting finding suggests that, in addition to typical chemical signals, mechanical forces in surrounding tissue are important for correct axon guidance, and suggest that a mechanosensative channel may be important. In a similar technological advance, Geoffrey Goodhill (University of Queensland, Australia) showed how their careful and in-depth timelapse analysis of axon growth cone morphology led to the discovery of oscillations in growth cone shape over time, and that these oscillations predict the eventual movement and guidance of the growth cone. Finally, exciting findings in enhancing CNS axon regrowth were shown by Frank Bradke (DZNE, Germany). By using a blood-brain barrier crossing drug to stabilize axonal microtubules, causing an accumulation of microtubules at the axon leading edge and axon regrowth, they were able to show functional recovery after CNS injury in rodents, an inspiring result in the difficult CNS environment.

The conference location in the historic Elphinstone Hall and New Lecture Theatre at the University of Aberdeen, surrounded by greenery and beautiful buildings, provided a tranquil environment for many enjoyable and productive discussions and informal chats over refreshments and during excellent poster sessions. On the last night, we were treated to the sight of dolphins swimming in the sea next to Aberdeen beach, during a drinks reception before a great Conference Dinner and opportunity to relax and socialise in the Beach Ballroom on Aberdeen seafront. This was followed later in the evening by a very active and enjoyable Ceilidh (traditional Scottish dance), ably assisted by our Scottish delegates.

I would like to thank the conference organisers and BSDB for providing this great opportunity for researchers to hear about and discuss cuttingedge and exciting research in the field of axon guidance and regeneration.

 

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I’m a Scientist, Get me out of here!

Posted by , on 25 October 2013

For those of you who haven’t heard of it before, ‘I’m a Scientist, Get me out of here!‘ is an online event that aims to connect school children with real working scientists. In the two weeks over which the event runs, the students get to interact with scientists online and ask them anything they like – from questions about their job and how they got to where they are today, to burning science questions they’ve always wanted to know the answer to. For example: ‘What is snot made of?’!

Scientists volunteer to take part and are allocated to a themed zone related to the area of science that they work in. For example, I worked on the cell biology of oocytes and embryos, so was placed in the Cells Zone. Throughout the event the students then get to vote for their favourite scientist. During the second week of the competition the scientist with the least vimascientist-logootes gets evicted each day, eventually leaving one winner – hence ‘I’m a Scientist, Get me out of here!’!

The main focus of the event is the fast and furious live online chats which take place a couple of times every weekday during the event. Up to 30 students and two or three scientists mean that you are literally bombarded with questions and lightning-quick typing is the order of the day. The many hours of my youth spent honing my keyboard skills by chatting on MSN messenger came in very handy here!

Outside of the live chats students can also log on to the website in their own time and pose yet more questions to the scientists. The questions really did come flooding in and ranged from ‘Why do we sneeze?’ to ‘How do cells come together to form an object?‘. For these questions, the scientists have a bit more time to consider the questions and give a more in depth answer. An important balance had to be struck between answering these questions in an engaging and informative manner without being too patronising and, most importantly, without slipping into the impenetrable jargon that we use so freely in our daily work.

A few times I had to resort to Googling to help answer some of the students’ questions and in doing so learnt some new things myself! For example I was asked ‘What is the unification of gravitation with quantum chromodynamics?‘. As a cell biologist, I’m not ashamed to say I had to look this one up!

Over the course of the event I also fielded a lot of questions about what I like to do for fun – such as ‘What football team do you support?‘. I expect the students were surprised (and relieved!) to learn that all the scientists had other interests outside of the lab. The ability to interact with scientists directly also helped to dispel some of the myths that scientists are all introverted geeks who can’t interact with other humans.

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I took part in ‘I’m a Scientist’ in November 2012 and had such a great experience it prompted me to explore other outreach and public engagement activities and now, one year on, I work in science engagement at the British Library. I would wholeheartedly recommend ‘I’m a Scientist’ to all readers of the Node – whether you are interested in outreach as an alternative career or if you just want to take step back and look at your research from a totally different perspective. It was refreshing to have to justify to enquiring students exactly how my research related to real-life – something that can be too easily lost sight of after long days at the bench. It also needn’t take up too much time – you can fit in the chats between experiments and then answer the offline questions in your own time. Although it really is very rewarding so I found myself checking for new questions throughout the day and eagerly awaiting the next live chat! All you have to do to sign up is write a one sentence summary of your research, which then gets judged by teachers and students…

 

 

Outreach logo new squareThis post is part of a series on science outreach. You can read the introduction to the series here and read other posts in this series here.

 

 

 

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Meeting deadlines for your calendar

Posted by , on 24 October 2013

calendar_monthThe next few months will see several interesting meetings, and deadlines are approaching. Here are some dates for your diary:

 

Registrations still available:

– The joint meeting of the French Society for Developmental Biology and the French Society for Genetics will take place in Avignon from the 12th to the 15th of November, and registrations are still being accepted. Cat from The Node will also be attending this meeting, and she looks forward to meeting any of you attending!

– The American Society for Cell Biology meeting in New Orleans will still be accepting registrations (no longer at reduced rate unfortunately!) until the meeting on the 14th of December.

 

Coming deadlines:

31st October: Abstract deadline for the EMBO workshop on mechanisms of neuronal remodelling. Registration deadline: 31st December (March, Israel)

4th November: Discounted abstract an scholarship deadline for Keynote Symposium on Cilia, Development and Disease. Discounted registration deadline: 7th January (March, California)

6th November: Abstract deadline for Keystone Symposium on Developmental Pathways & Cancer and Stem Cells & Cancer. Discounted registration deadline: 3rd December (February, Canada)

7th November: Abstract deadline for Keystone Symposium on Plant Signalling. Discounted registration deadline: 5th December (February, Colorado)

5th December: Discounted abstract and scholarship deadline for Keystone Symposium on Epigenetic Programming and Inheritance. Discounted registration deadline: 4th February (April, Massachusetts)

9th December: Abstract deadline for the Annual Drosophila Research Conference. Discounted registration deadline: 21st January (March, California)

10th December: Discounted abstract and scholarship deadline for Keystone Symposium on Stem Cells & Reprogramming. Discounted registration deadline: 6th February (April, California)

13th December: Registration deadline for RIKEN CDB Symposium: Regeneration of Organs (March, Japan)

 

– Registration is also open for the BSCB/BSDB joint Spring Meeting, which will take place in March at the University of Warwick. Early bird registration deadline is the 7th of February.

 

As usual you can check the full list of meetings in our events calendar, and you can add your own meeting if you are a registered as a user.

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How to spot a stem cell…

Posted by , on 23 October 2013

 

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Here’s a basic but really important question… how do stem cell scientists actually identify the stem cells they are raving about? We have all heard that we have stem cells in our gut, in our skin, in our eyes or in our brain for example, but scientists are still looking for stem cells in other tissues.

To understand how scientists go about spotting stem cells in adult tissues we have to remember what a stem cell is. A stem cell is a cell that can make copies of itself, a process called self-renewal. A stem cell is also a cell that can specialize into the cell types of its own tissue, a process called differentiation. For example, blood stem cells have to self-renew to maintain their reservoir in the bone marrow, but also produce daughter cells that specialize exclusively into all the types of blood cells (red blood cells, immune cells, platelets,…). So when scientists are looking for stem cells, they basically are looking for cells that comply with these criteria.

In order to look for such cells, most “stem cell spotting” studies use an in-vivo lineage trace experimental strategy. A recent example of this was a study published in Cell Stem Cell, in which Andoniadou and colleagues have identified a pool of stem cells in the adult pituitary gland. In a nutshell, they use fancy genetic engineering method to tag cells that express the protein Sox2 with a fluorescent protein, which makes them able to visualize these Sox2 positive cells. After the initial “tag” step, the researchers wait for a few months and can then see the cells that have been produced by the original Sox2 positive cells. This works because the daughter/grandaughter/great-grandaughter cells also have the fluorescent tag, passed down through generations of dividing cells.

In the upper right picture of this panel, one can see that 48 hours after the “tagging” step, the majority of Sox2 cells (in red) are also tagged with the fluorescent protein (seen by α-GFP, in green), so that the cells appear yellow (arrowheads). The other pictures in the panel have all been taken 9 months (mo) after the initial tagging of the Sox2 positive cells. One can see that some “tagged” cells (in green) still express Sox2 (yellow cells, arrowheads), indicating self-renewal. In the other pictures, some “tagged” cells (still in green) also express proteins such as SOX9, PRL, GH, TSH, GSU, LH, and ACTH (yellow cells, arrowheads), which are proteins that are expressed in the specialized cells of the pituitary gland, indicating differentiation. So from these observations, the authors conclude that, during the 9 months after tagging, some of the original Sox2 positive cell population has self-renewed (because some progeny still express Sox2) and differentiated into the specialized cell types of the pituitary gland (because some progeny express a battery of differentiation markers). This tells us that the original cell population is a stem cell population!

Though this lineage tracing strategies are fairly complicated and time consuming, this is how many scientists spot stem cells in our bodies!

 

Picture credit:

Andoniadou, C. L., Matsushima, D., Mousavy Gharavy, S. N., Signore, M., Mackintosh, A. I., Schaeffer, M., Gaston-Massuet, C., Mollard, P., Jacques, T. S., Le Tissier, P. et al. (2013) ‘Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential’, Cell Stem Cell 13(4): 433-45.  doi: 10.1016/j.stem.2013.07.004.

 

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PhD Scholarship in Developmental and Regenerative Dermatology Laboratory at UNSW, Sydney, Australia

Posted by , on 22 October 2013

Closing Date: 15 March 2021

UNSW crest

 

 

 

 

 

Developmental and Regenerative Dermatology Laboratory

School of Medical Sciences, University of New South Wales

 

PhD Scholarship

The Developmental and Regenerative Dermatology Unit is seeking a highly motivated and enthusiastic postgraduate student for a research project in skin (cancer) biology.

 

Recently, we made the pivotal discovery that Yes-associated protein (YAP) functions as a key molecular switch in epidermal stem/progenitor cell proliferation and differentiation (Beverdam et al., JID 2013). Currently, we are investigating the developmental genetic context in which YAP functions to control skin stem/progenitor cells in normal and in disrupted skin biology, and the PhD student will participate in this research.

 

We employ genetically manipulated mouse models, human skin samples, advanced imaging technology such as confocal microscopy and whole mouse in vivo imaging, gene and protein expression analyses and whole genome approaches to address our research questions.

 

Outcomes of our research will open up exciting new avenues for translational research and the development of treatments for human regenerative skin disease.

 

For more info on the laboratory: https://research.unsw.edu.au/projects/dr-annemiek-beverdam

 

Award: Scholarships are valued at $24,653 per annum (tax exempt), and may be renewed for up to three years, subject to satisfactory progress.

 

Eligibility: All applicants must hold an Honours degree or equivalent in a related biological science (e.g. Developmental Biology, Genetics, Cell Biology, Pathology). Applicants should have a particular interest in the project on offer and have experience in histology, molecular biology techniques, cell culture, bioinformatics and mouse handling.

 

Application Process: Applicants should include the following documents

• Cover Letter

• Curriculum Vitae

• Copy of an academic transcript

• Names and contact details (email address and phone number) for at least 3 referees.

 

All applications should be emailed to Dr. Annemiek Beverdam: A.Beverdam@unsw.edu.au

 

 

 

 

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Evo Devo Art

Posted by , on 21 October 2013

I make art that brings together music, animation, and performance to explore evolutionary and developmental biology themes. I aim to illuminate the magic of the biological world for a broad audience of scientists and non-scientists, young and old. In order to communicate science to the general public and fuel a sense of awe at the natural world, I intertwine biological stories with classical narratives and human emotion, and I create multimedia experiences that allow an audience of diverse backgrounds to have different entry points—musical, visual, theatrical, or scientific—to the experience. Here’s a trailer from my performance Theory of Flight, where a lecturing scientist reveals she’s been growing her own wings using avian genes, and animations and music bring the transgenic processes to life.

I was introduced to many of the evolutionary and developmental biology (evo-devo) themes featured in my work while studying biology at Yale, and while working in Dr. Antónia Monteiro’s lab. When the Node asked me to write about how I go about scientific outreach, I thought a dialogue with Dr. Monteiro would be the perfect way to delve into the process of bringing biological ideas to a broad audience.

Many thanks to Dr. Antónia Monteiro, Associate Professor, Yale-NUS-College and Department of Biological Sciences, National University of Singapore.

 

Dr. Antónia Monteiro (AM): Anna, you have a bachelor’s degree in biology from Yale University and have published your senior thesis project in the field of evolution of development. But you went on to pursue a masters degree in electronic arts. Did you ever think about a career in science? And if yes, what was it about it that did not quite satisfy you? 

Anna Lindemann (AL): There were certainly times when I imagined pursuing a more traditional scientific career, but my life seems to be an experiment with an ever-shifting protocol. I exist in a hazy territory between art and science. This means that sometimes I feel lost—I am a “science” person around “art” people, and an “art” person around “science” people. But at the best times, this hazy territory is an exciting place to be, full of possibilities and new connections, whether that’s connecting disparate disciplines to generate new forms of creative output, or whether that’s connecting other people to new ideas that lie outside of their area of specialization.

 

AM: I have seen several of your performances. You are very creative with your use of music, performance, audio-visuals, etc. What is going on in your head when you are planning a new piece? Do you think first about the science you want to communicate? The music you want to use? How do you go about pulling it all together?

AL: My approach to integrating artistic and scientific disciplines is twofold. I am interested in illuminating biological processes, especially evo-devo processes, for a broad audience, and I am also interested in developing art using biological processes as a model for creation.

So, sometimes I am thinking about the most effective visual or musical elements to convey a particular biological story in an engaging, dramatic, or humorous way. And sometimes I am trying to create interesting, new, complex, absurd, and beautiful sounds and images, and I turn to biological processes in order to do that, processes that have evolved over millions of years to create interesting, complex, absurd, and beautiful life forms. To this end, many of my projects include music that has been developed algorithmically based on developmental biology. I am currently exploring a new way of developing music generated from the dynamic gene expression output of gene network simulations.

Ultimately, how the musical, theatrical, visual, and biological parts come together involves a lot of trial and error, and is certainly far from an efficient or direct assembly process.

 

AM: The evo-devo science behind your pieces is state-of-the-art and complex, yet, you manage clearly to convey the big picture to a broad college-educated audience. How do you go about picking the evo-devo themes for your performances? And shaping them for a broad audience?

 AL: I first learned about many of the evo-devo themes featured in my work, including the modularity and co-option of genetic networks, through your evo-devo course, other courses I took at Yale, and the experience of working in your lab. The thesis research I did in your lab investigating the role of the Hedgehog signaling pathway in butterfly eyespot development was a significant influence on the investigations that the main character pursues in my performance Theory of Flight. Once I start developing a project, I also read a lot of scientific journal articles. People have commented that Theory of Flight is the first performance they’ve seen with a program that has citations.

There are a few things that stand out in terms of shaping the evo-devo themes for a broad audience. First, I want audiences to leave with a sense of wonder and appreciation for the evo-devo processes that give rise to the complex biological world. I want an audience to have that same contagious sense of awe that I remember feeling when first learning about evo-devo from you, the sense that all of the growing and evolving that organisms do is mysterious and incredible. Keeping a sense of awe in the foreground, and mechanistic details in the background involves lots of revisions of a project for me. Even though I create fictional narratives, I want the science behind those narratives to be detailed and realistic. I constantly have to reign in the tendency to bombard and overwhelm an audience with details that would ultimately dissuade rather than encourage them from engaging the evo-devo themes.

Second, I think about connecting the evo-devo themes to universal human experiences. In Theory of Flight, the exploration of the developmental mechanisms of wing growth and the evolutionary origins of flight are framed within the context of a character’s quest to develop her own flight. An audience can relate on some level to the character’s ambitious striving, failures, and isolation, even if perceiving the world through a biological lens is something new to them.

Third, I embrace a multimedia mindset. I believe that bringing together performance, music, and animation not only allows for evo-devo themes to be explored in a variety of ways, but also connects to a diverse audience by providing multiple entry points to the performance. For some audience members, the biology may be familiar, but the theatrical and musical context might be unfamiliar. For other audience members, the animation or music or performance might be familiar territory and the biology foreign territory.

 

AM: Writing, performing, and then trying to “market” your product must be challenging. Are there organizations or venues that can help people like you, at the intersection of performance art and science, get more visibility? Have you thought about ideal venues for how artists/scientists like yourself should be interacting with the rest of us? 

AL: I am excited by the growing number of venues, series, events, and institutions that are interested in supporting work at the intersection of art and science. I’ve had a wonderful time working with some of them.

Theory of Flight was premiered at one of the black box theaters equipped with state-of-the-art multimedia performance technology at Experimental Media and Performing Arts Center (EMPAC) in Troy, NY. EMPAC opened to the public in 2008 as a place “where the arts, sciences, and technology interact with and influence each other by using the same facilities, technologies, and by breathing the same air.”

I’ve performed at the Entertaining Science series in New York City which pairs lectures by prominent scientists with performances by diverse artists. Entertaining Science started in 2002 as a monthly series organized by chemist and poet Roald Hoffman of Cornell University and neuroscientist and composer Dave Soldier of Columbia University.

I’ve presented at a marathon “Survival of the Beautiful Wonder Cabinet” organized by David Rothenberg that brought together artists and scientists that think about aesthetics and evolution in their work. And I’ve presented through the Franke Program in Science and the Humanities that started this past year at Yale.

I also work with high school students to think creatively across the arts and sciences through a program called the ArtScience Prize, which is part of a larger international organization of educational programs and exhibition spaces that focus on the creativity that can emerge from interdisciplinary investigation.

There are many other places around the world, far too many to name here, that celebrate art-science intersections in various ways, and many that I hope will continue to form. I am always interested in new presentation contexts that may or may not have an explicit mission to integrate art and science, and that might have resources and budgets big and small. For example, I would love to some day perform at a biology conference.

I think there are still many untapped possibilities for how art and science can come together to spark new forms of understanding and creativity, and to be meaningful for artists, scientists, and the generally curious.  I’m interested in how venues like the Node can foster this kind of interaction online, and I’m interested to hear from readers of the Node about their experiences in art-science intersections (either as participants or observers), and their visions for future cross-disciplinary activity.

 

 

Outreach logo new squareThis post is part of a series on science outreach. You can read the introduction to the series here and read other posts in this series here.

 

 

 

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Neocortex evolution and human uniqueness

Posted by , on 20 October 2013

“So God created mankind in his own image, in the image of God he created them; male and female he created them. God blessed them and said to them, ‘Be fruitful and increase in number; fill the earth and subdue it. Rule over the fish in the sea and the birds in the sky and over every living creature that moves on the ground.’”

The concept of human uniqueness may be about as old as man himself.  We have long regarded ourselves as somehow special and different from all of the other animals.  This attitude is clearly reflected in the above creation story: there is man, crafted in the image of God, and then there is the rest, put here to be ruled over and fed upon.

The world and our understanding of it have changed quite a bit since those words were first penned, but the human uniqueness obsession remains.  For one, we now attribute most of our uniquely human attributes to our highly developed neocortex.  Numerous lines of evidence suggest this structure is critical for our cognitive abilities, higher order sensory processing, memory, and personality.  But we are not the only creatures with a neocortex. In fact, all mammals have one.  What then, sets us apart?

The Company of Biologists recently hosted a workshop, titled “Evolution of the Human Neocortex: How Unique Are We?,” in response to flourishing research on human brain evolution.  Exactly what makes us special is hardly a trivial question.  Thirty evolutionary neuroscientists were gathered in West Sussex, UK, cloistered for four days to discuss that which makes us human.  And at the end of it, I believe we are scarcely closer to providing a satisfying answer.

A theme of the workshop was the apparent conflict between “Humans are just like the other animals” and “Humans are self-evidently special.”  As biologists, we are keen to spot similarities between even distantly related animals.  The very use of model organisms to study issues related to human biology depends on this.  Much of our knowledge on neocortex development, for instance, comes from mouse and we extrapolate this to our own brain.  We have a neocortex, but so do all mammals.  Ours is elaborately folded, but so is the sheep’s. Our neocortex is huge, but it’s not a special kind of huge.  As Barbara Finlay pointed out, it’s just as large as one would expect for our body size, given mathematical brain scaling models.  The astonishing neocortex of dolphins and whales reminds us that we are not alone in being big brained.

On the other hand, mice don’t host conferences on brain evolution.  Several speakers emphasized the obvious, and profound, gulf in cognitive abilities between humans and non-humans.  So if humans are not unique in terms of gross morphological organization, we may need to closely examine the more subtle aspects of neocortex biology.  Frank Polleaux brought an interesting perspective to the discussion: perhaps human cognitive abilities are not a result of neuron number or brain size, but rather of fundamental differences in neuronal properties.  His lab’s work on the srGAP proteins illustrates this point nicely.

Gavin Clowry made a similar point with respect to neocortical GABAergic cells.  Humans, so far as we know, are the only species to produce inhibitory interneurons locally in the cerebral cortex.  We don’t know how or why this happens, and it may simply be to provide the expanded excitatory cell population with an appropriate balance of inhibitory cells.  GABA cells in humans, however, may have undergone physiological innovations for coordinating oscillatory behavior across the brain.  One particular class, the chandelier cell, is unusually abundant in our brain.

John Kaas discussed the tremendous proliferation of neocortical areas, a key dimension of neocortex organization, in humans.  While the stem mammal likely had a tiny neocortex with an estimated 20 areas, modern man has about 183 distinct areas or more.  Morphologically or physiologically differentiated areas may translate into a greater diversity of information processing.  More areas may allow us to extract more useful information from finite sensory input, or provide more behavioral flexibility.

The human brain is an impressive piece of work, and while we are justifiably fixated on our uniqueness, we must not forget our place in the world.  The idea that we are the pinnacle of some great chain of being is long dead.  Rather, our body and mind are just as adapted to our particular circumstances as those of any other extant animal, and have been adapting for just as long.  Our neocortex is big and sophisticated, but some of its key cellular components can be found in reptiles and birds and have been around for a very long time.  The story of our evolution is just one of millions of such stories, and through the power of comparative biology we can infer the key details of its plot.

Edit:

There was a lot of great science presented and discussed at this meeting, and regrettably I can’t talk about all of it here.  Katherine Brown posted earlier about the meeting (see comment and link below, thanks Cat!).  A list of speakers and brief description of the meeting can be found here: http://workshops.biologists.com/workshop_sept_2013.html.  Information on the srGAP proteins from the Polleux lab can be found here: http://www.sciencedirect.com/science/article/pii/S009286741200462X.

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Categories: Discussion, Events

BSCB/BSDB 2014 Meeting- Registration is now open

Posted by , on 18 October 2013

Registration for the 2014 BSCB/BSDB Meeting to be held at the University of Warwick on the 16th-19th of March is now open.

The meeting includes plenary talks from Janet Rossant and Kai Simons. Full program and registration is available from,

http://www.bscb-bsdb-meetings.co.uk/default.htm

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Categories: Events, Societies

An interview with Janet Rossant

Posted by , on 18 October 2013

This interview first appeared in Development.
 

Janet Rossant is a developmental biologist who has worked for many years on the mouse blastocyst, the derivation of stem cell lines and on investigating the mouse genome. In June 2013 she became the president of the International Society for Stem Cell Research (ISSCR). At the 2013 International Society for Developmental Biology (ISDB) meeting, Janet was awarded the Harrison Medal – a prestigious prize given only once every four years.

 
At this ISDB meeting you were awarded the Harrison Medal, a very prestigious prize for developmental biologists. What does it mean to you to be awarded this prize?

It was obviously a great honour. It is really nice when you are recognised by your peers and when the whole international community gives you the prize. Following in the footsteps of other great scientists is both awe inspiring and intimidating.

Jane Rossant croppedOne of the previous awardees of the Harrison Medal was Sir John Gurdon, who lectured you when you were an undergraduate at Oxford and who you’ve said inspired you to become a developmental biologist. How did he influence you, and have there been other mentors who influenced you at different points in your career?

As an undergraduate studying zoology I did everything from animal behaviour to ecology, evolution, development, cell biology and biochemistry – it was a very broad course. I knew that I was interested in biology, but the question was what aspect? John lectured to us not long after he had done his cloning experiments. They were so important, really illustrating how the genome is the same in all cells. That opened up another question: if the DNA is the same in all cells, how is it that cells become different during development? This is such a simple question, but one that can keep you going for a long time. I was just fascinated. We also had a few lectures by Chris Graham, who had just joined the Zoology Department and was starting to do similar studies in mouse embryos. These made me think: ‘mice are really like us!’, and this seemed a fascinating new direction. So it was a combination of John’s overall developmental biology and hearing from Chris about mice as a model system that got me into the field.

Later on, when I moved to Canada, I had to go out and find people to help me. There were two people there who probably aren’t very well known now. Verne Chapman, a mouse geneticist in Buffalo, was really my support structure when I first came, making sure that I got invited to meetings and so on – creating that initial network; and Tom Wegman, in Alberta, was also a person who introduced me to various people and really helped out. They both died young, which is very sad, but when I look back I realise how important they were for me.

 

In your career you have worked mainly with the same topic and model organism, which is very rare nowadays. How have you maintained this focus for so long?

I am very unusual in that I mainly stuck with the same question (how to make a blastocyst) and the same species throughout. I have been lucky in that I have been able to diversify by collaborating. Although we have been interested in similar problems for many years, we have always been seeking new technologies – either bringing them in or implementing them ourselves. I think that is how I have been able to stick with the same general question and yet always keep making advances. In particular, I have been very actively involved in a major mouse genome mutagenesis project, which is a different way of thinking about doing science. I work on lots of things, but what do I love? Of course it’s the embryo – I still want to understand the early embryo.

 

What is the next big scientific challenge that you would like to tackle?

I still think that we can do quite a bit more to understand the blastocyst. I believe that it is a system that needs to be studied at the single-cell level, with the combination of imaging tools, single-cell gene expression analysis and computational modelling. The mouse blastocyst is a system in which we can really gain a core understanding of how cells develop until a point at which their fate is restricted. It only has three cell types, development happens slowly, you can grow it in a defined culture system and watch it all the way through. So I’m still pursuing that same question I started out with: I don’t know if this is good or bad, but it’s true. After all these years, I still haven’t solved it!

 

There is a lot of discussion at the moment about the relationship between stem cell research and more traditional developmental biology, specifically whether stem cell science is a separate field or a branch of developmental biology. Where do you stand in this discussion?

I have just become the president of the ISSCR and was the president of the Society for Developmental Biology (SDB) in the late nineties. I think there is no question that the basic biology of stem cells sprang out of developmental biology. But stem cell research is more than just the basic science of stem cells these days – it is a more applied branch. Any stem cell meeting is going to have a core of talks on the basic developmental biology of stem cells, but is also going to have talks about bioengineering, ethics and clinical applications. At the same time, a developmental biology meeting is going to have talks on stem cells, as a fundamental aspect of developmental biology, but is also going to have talks on morphogenesis, evo-devo and all sorts of other interesting things. There is an overlap, but I don’t think a merger between the fields makes sense – we just need to take advantage of both. Certainly, as president I am going to make sure that developmental biology remains a part of the ISSCR.

 

As ISSCR president, what are your objectives, what challenges do you think you will face, and how does it compare with your past presidency of the SDB?

The ISSCR is a relatively new society, only founded in 2003, although it has grown considerably since then. As a scientific society, the primary objective is to make sure that we have a great annual meeting in the same way that the SDB does. I think that is the number one role of the president, with the help, of course, of the programme committee.

The ISSCR is an international society, and there is no American or British society for stem cell biology. With stem cells so much in the public eye, the ISSCR is in a unique position to be the rational voice for stem cell research worldwide. Over the next year, we plan to develop a communication strategy so that we do more in terms of public education and outreach to patients and families. We aim to do this in partnership with national networks because things are different in different nations. I also want to have a rapid response team for when things come up in the newspapers, such as the Italian stem cell issue [the use of unproven stem cell therapies in Italian hospitals]. We need to have a more proactive set of principles and guidelines that drive our positions on these issues, rather than doing things on an ad hoc basis.

One of my other goals is to make sure that the society is not too US-centric. We have board members from all over the world, but we don’t have formal connections with local groups in Japan, Europe or Canada. We need to develop these relationships, so that we can deal with any issues as they arise. The local networks also have very good public education tools and know what is good for their audiences.

 

You have been involved in a lot of public discussions on the ethics of stem cell research. What do you think are the responsibilities of scientists in participating in this kind of discussion?

I think is very important for established scientists, who have a strong reputation in the field, to stand up and be counted. We have to make our views known at all levels, from government to the public. Public education is extremely important, and we should get out there and try to educate the public, particularly in the stem cell area. I would say that the debate around the ethics of the use of human embryos has largely moved on. But we are still facing major ethical concerns in the stem cell area, particularly now with stem cell tourism and unproven therapies appearing all over the world. The ISSCR has really taken this on as an issue, but it is a very difficult one because the environment is in constant flux. We have to think again about ways to educate the public, patients and their families by trying to explain to them what it means to have a valid therapy and how to be very careful when they explore therapies offered by clinics that are springing up around the world.

But we have to recognise that patients want hope, and if their doctor tells them that there is none then they will go to a clinic where they think there is hope. We have to provide support and give them hope. For example, even when parents and families know that their child is not going to survive, if they are told that their child can be in a research study and help others then they are usually very willing to be involved. There is a sort of hope for the future, and there is of course the possibility that, maybe, they will be lucky. And that is ok, so long as you put it very clearly to them that there is no guarantee that the trial therapy is going to work. But unregulated clinics that claim to be able to treat incurable or major debilitating diseases are potentially dangerous and certainly unethical in terms of charging people for unproven and risky treatments.

 

Do you think that PhD students and postdocs should take part in a more local discussion?

Yes, we should take the opportunity to talk about stem cells at all levels. So I would say to early career scientists that they should explain what they do when they play baseball with their local team, to their grandmother, anywhere they go. We send a lot of graduate students into schools to give science talks, and we have stem cell talks organised by graduate students and postdocs where we bring in high school students. For a big professor to go into a school and pontificate is not so good, but high school students are closer to graduate students and can relate. But senior scientists absolutely have a duty to go to governments and regulators to make their positions known.

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Categories: Interview