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Transparent mouse embryos and hematopoietic cell clusters

Posted by , on 8 November 2010

I was lucky in graduate school and my postdoctoral research—I was a microscopist working on a transparent organism (C. elegans).  Some microscopists don’t have that luxury, but have developed amazing techniques in order to visualize development in organisms such as mice.  In the November 1 issue of Development, Yokomizo and Dzierzak use a technique that makes an entire mouse embryo transparent and ready for high-resolution confocal microscopy, and they describe a comprehensive analysis of hematopoietic cell clusters.

Hematopoietic cell clusters are bunches of cells found on large blood vessels in mouse embryos and play an important role in the development of the adult blood system.  Based on earlier reports, it was believed that hematopoietic cell clusters contained hematopoietic stem cells (HSCs), which give rise to many blood cell types.  By using a whole-mount transparency method and 3D reconstructions of a mouse embryo, Yokomizo and Dzierzak constructed a temporal and spatial map of all hematopoietic clusters.  The number of clusters peaks at embryonic day 10.5, and the clusters are found in specific subregions on vessels.  In addition, Yokomizo and Dzierzak show that some clusters do contain HSCs and progenitor cells, confirming the pivotal role of cell clusters in the formation of the adult blood system.

Images above show hematopoietic cell clusters on the aorta in mouse embryos.  CD31 (magenta) is expressed by both the endothelial cells on the aorta and clusters cells, while c-Kit (green) is expressed only by cluster cells.  The high magnification view of the cluster on the right shows how closely the clusters are situated next to the endothelium of the aorta.

ResearchBlogging.org

Yokomizo, T., & Dzierzak, E. (2010). Three-dimensional cartography of hematopoietic clusters in the vasculature of whole mouse embryos Development, 137 (21), 3651-3661 DOI: 10.1242/dev.051094


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the Node update – writers, thumbs, polls, and emails

Posted by , on 8 November 2010

Writing for the Node
Have any of the entries on the Node inspired you to add something yourself? Go ahead! We’d like to remind you that you don’t need to ask permission to write for the Node. You also don’t need to wait for us to ask you to write something – although we might. All you need is an account, and you can write once, twice, or however many times you like.

If you would like to write for the Node, but don’t know what to write about, just let us know and we’ll give you some ideas.

Node posts are read by developmental biologists across the world, and are regularly featured on the front page of the Development website.

Thumbs up/down
We have now implemented thumbs up and thumbs down icons on comments as well as posts. This is an especially good way to let us know whether you liked a post or comment, so please make use of this feature. It takes less than a second to click one of these images, and it gives us a lot of information about what type of content you like to read.

Polls
We have added a new feature to include polls in posts. In the future we will use this for specific interactive features, but now I’m going to use it to re-ask this question about the format of email notifications. (See below).

Email notifications
Did you know that you can receive Node posts directly to your inbox? Currently, email updates about new Node posts arrive as a “daily digest”. It’s also possible to set these updates to occur after every post and have users select which categories they would like to receive in email. In that case, if you only want email notifications of interviews, or everything except job ads, you can change those settings. (The choice between digest or per-post cannot be made at the individual user level, unfortunately, so we have to make one decision for everyone.)

Are you currently using the e-mail notification service, or would you use it if it was in a different format? Please let us know via this poll:

(poll closed and archived)

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Categories: News

SfN meeting: a 21st century event

Posted by , on 3 November 2010

conference venue: the San Diego Convention CenterThe annual meeting of the Society for Neuroscience kicks off in San Diego at the end of next week, and there are a lot of interesting updates even for people who, like me, are sadly *not* attending.

First of all, if you’re planning to go but haven’t yet registered, you can register on site, but it’s cheaper to register online, even this close to the actual event.

The SfN has also once again selected dedicated “Neurobloggers” to cover the meeting, so you can follow their blogs for updates during the entire conference. For the “development” track of the meeting, the official SfN bloggers are Anahita Hamidi at Genetic Expressions, and Jason Snyder at Functional Neurogenesis. Big congrats to Anahita and Jason. I’ll be following their updates and will be sure to highlight them on our Twitter account once in a while.

Speaking of Twitter, the SfN is also encouraging attendees to use Twitter to talk about the meeting, using the official #sfn10 hashtag, and they have their own account as well. This is truly 21st century conferencing!

In an independent effort, two members of Labspaces have planned a get-together for Twitter-using attendees of the SfN meeting. They’ve called it B.A.N.T.E.R. (“Bloggers and Neuro-Tweeps Engaging Recreationally” – you can always spot biologists by their propensity for far-fetched acronyms…) and it will occur on the evening of November 15, right in the middle of the conference period. More info here.

It seems that, even though I can’t be there, I’ll still be able to follow the entire meeting online, down to the social events! If you are there, don’t forget to drop by the Company of Biologists’ booth to say hello. (A helpful insider tip: our best swag always runs out on day one at big meetings, so visit early!)

And if any Node readers applied to be an SfN blogger but didn’t get selected, remember that you can always write for the Node if you want to reach a large audience of scientists!
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A primer or two in collegiality and mutual benefit

Posted by , on 2 November 2010

Community resources are usually only as good as the people who use them are numerous and virtuous.

Despite my best intentions, there are not enough incentives out there for me to spend my time validating and then manually entering human SNPs, that I’ve found during the course of my sequencing various candidate genes for diseases, in the fantastically useful dbSNP database. However, with the advent of high-throughput sequencing and the possibility for large-scale genome annotation, I don’t think that my lack of participation makes such a difference.

It is otherwise with respect to designing and validating primers for PCR. Oh, and if you ever have to teach a trainee about PCR, have a go at the fabulous teaching resources provided by the Cold Spring Harbor Laboratory. Like this pretty video I can’t seem to embed, but you can look at here.

Anyhow, I wanted to draw your attention to RTPrimerDB. It’s been around a number of years, and has been the object of three readily accessible publications in Nucleic Acids Research as a community resource.

About half of the primers are for human gene expression assays of various types, but there are as of today, more than 800 primers for mouse PCRs of various ilks. I found some to my liking today.

So, in my laboratory, I keep a spreadsheet with a tab for human, a tab for mouse and a tab for chicken. Into this I have added, somewhat indiscriminately and in the order in which they arrive, primers for genomic DNA or cDNA amplification or both, and specify whether or not they are intended for quantitative or end-point PCR. Actually to be brutally honest, I haven’t developed any primers for qRT-PCR for the chicken.

I write on a regular basis to authors who are not among those who increasingly do include their primer sequences in their article submissions, because I am under the misguided illusion that I will save time by using assays that have already been validated by someone else.

Woe is me when I presume such a thing. Housekeeping genes as standards are particularly notorious, but many is the time when I have either blindly ordered primers according to publications and then been surprised at inefficient amplification under the more-or-less specified conditions, or a poor melting curve, to find that even in silico they shouldn’t have worked.

So, here’s to saving a little time and checking in silico.

The first suggestion is to check that your genomic DNA primers will amplify what you expect. For this, I enjoy using the simple PCR module on UCSC’s (wonderful) Genome Browser. You check that you are using the right organism, and sometimes the right “build” – that is, the right version of the genome sequence against which to check, and the rest is self-explanatory. Sometimes it is also nice to double-check primers that span exons, in case you do get some genomic amplification because of contamination, and to see what the expected size would be if that happened.

The second, is to make use of Primer-BLAST. You know this resource – or should, if you don’t yet:

Primer-BLAST was developed at NCBI to help users make primers that are specific to the input PCR template. It uses Primer3 to design PCR primers and then submits them to BLAST search against [a] user-selected database. The blast results are then automatically analyzed to avoid primer pairs (all combinations including forward-reverse primer pair, forward-forward as well as reverse-reverse pairs) that can cause amplification of targets other than the input template.

So, what I didn’t know, but is perfectly lovely, is the following: Primer-BLAST can check those published primer pairs for you without specifying their target.

That is, you skip the whole first section about PCR Template, and go right to Primer Parameters > Use my own forward primer (and reverse, natch). You don’t have to play around with anything about length or melting temperature, but you scroll right down to Primer Pair Specificity Checking Parameters.

I only change Organism if needed. There are automatic fill-in fields that you need to give a little time to suggest, when you start typing eg. Mus musculus. When I have had doubts as to whether authors who carried out xenotransplantations actually posted their host or their donor amplification sequences, I use the link “Add more organisms” and away we go. Leaving RefSeq RNA (refseq_rna) for the Database is usually fine for checking RT-PCR primers, but there are other options. Like “nr” if you want to play it safe (but it takes slightly longer, of course).

For example, let’s say I want to know for sure what part of the Xenopus Chd7 protein was used to make a recombinant peptide to immunize rabbits and develop the polyclonal antibody used in this publication. I don’t specify whether I want Xenopus laevis or tropicalis, but stick with the genus only.

As a result, I find out that the 30-bp primers provided in the Methods section amplify perfectly and exclusively, a 549-bp fragment of “>NM_001091800.1 Xenopus laevis chromodomain helicase DNA binding protein 7 (chd7), mRNA” – and by following the link, I can figure out which part of the protein it would be. I also know the predicted melting temperatures, giving me an idea of conditions, and alternative amplifications either in other species (Xenopus tropicalis, with a single nucleotide difference in each primer) or in other parts of the genome (just try checking standard primers used against Gapdh sometime). I’ve often seen such single nucleotide differences, which can mean the difference between a PCR that works and one that doesn’t. Typos do happen. Another thing that happened to me today was that I noticed that of the two housekeeping gene primer pairs provided in a publication, the two genes were supposed to amplify with the same primer pair – a simple cut/paste error. While waiting for a response from the authors, perhaps who would have to ask a postdoc long gone from the lab, one can easily find out which one it is.

Then of course, you can make up your mind as to whether you really want to order primers on the basis of confidence in such a lab’s ability to optimize all the parameters. But that is another story for another day.

Meanwhile, I would be eager to find out the following:

1. How do you keep track of PCR primers in your lab, for any use including that of making templates for in vitro RNA probe transcription?

2. Do you annotate as to whether or not they work, or more subtly, the conditions tried for optimization?

3. Do you systematically ensure that primers appear somewhere with publications that use them, either as cited references, tables or supplementary material, or online on your lab website?

4. If you work in a non-muring, non-human, non-Arabidopsis, non-Oryza kind of model organism, are there other similar public resources of PCR primers? Because aside from these, hardly any other organisms are represented in RTPrimerDB. There are something like 5 pairs for Drosophila or Danio, for example.

Ooh. I see there is a “Poll” tab in my author possibilities, but I don’t know how to use it further. Meanwhile, comments and discussion will be much appreciated.

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An interview with Shinichi Aizawa: President of the Japanese Society of Developmental Biologists

Posted by , on 29 October 2010

(This interview previously appeared in Development)

This August, the Society for Developmental Biology (SDB) held their annual meeting in Albuquerque, New Mexico, USA, jointly with the Japanese Society of Developmental Biologists (JSDB). The JSDB has recently increased their international profile under the presidency of Dr Shinichi Aizawa from the RIKEN Center for Developmental Biology (CDB). We caught up with him at the SDB/JSDB joint meeting to discuss the projects that the JSDB has been undertaking under his leadership to expand the activities of the society beyond the borders of Japan.

What are you working on at the moment?

I’m interested in head development, specifically focussing on questions ranging from anterior-posterior axis formation to the early regionalisation of the brain. I have generally used a mouse genetics approach in this work, but I have also become interested in phylogenetic aspects, and am working with non-model animals such as Suncus, pig, gecko, soft-shelled turtle and the lobe-finned fish Polypterus.

How long have you been President of the Japanese Society of Developmental Biologists?

I’ve been president for four years. At our society, the president of the society and chairman of each annual meeting are two separate positions. The president and board (14 members) are elected by the members of the society, and their terms last for up to four years. The president nominates the chairman of the annual meeting with the agreement of the board members. I understand that this is different from the structure at the SDB, where the society president is also the head of the annual meeting.

How old is the JSDB?

The society was founded in 1968, and we currently have approximately 1400 members. More information can be found on the JSDB web site.
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WormBase: It’s not just for C. elegans anymore

Posted by , on 29 October 2010

WormBase — wormbase.org — is the central data repository for Caenorhabditis elegans and related nematodes.

C. elegans is a well-known system for studying problems in developmental biology, the benefits of which I will quickly rehash here. Its rapid generation time from fertilized egg to gravid adult (3.5 days) and small size (1mM) permit 1000’s of animals to be grown on a single plate in short order. As a self-fertilizing hermaphrodite, isogenic populations can be generated from a single animal. And the presence of occasional males permits standard crosses to create different genetic backgrounds. Moreover, the complete (and invariant from worm to worm) developmental lineage and neuronal connectivity are known. Thus C. elegans is an ideal system in which to conduct genetic screens looking for mutations that specifically disrupt developmental processes. Comparison to the baseline lineage and neuronal connectivity can provide quick insight into gene function, and standard genetic techniques can be used to identify interacting or regulatory genes.

WormBase supports the use of C. elegans as a model system by collecting and annotating experimental data from the published literature. By placing these data in a rich intellectual framework, WormBase facilitates further discovery that may not be readily apparent from studying the data in isolation. For example, WormBase gene summary pages contain manually curated, concise descriptions of the gene, which report gene function (summarized from null phenotype analysis when available), expression patterns, ortholog assignments,  and link to OMIM (Online Mendelian Inheritance of Man) if predicted orthologs are associated with genes involved in human disease. These pages also display phenotype data based on both mutant analysis and RNAi knockdown experiments. Further, these gene pages display the results of in-house homolog analysis using a number of different analysis tools: BLASTP, Inparanoid 7, Compara and TreeFam. Finally, WormBase is an active member of the GO Consortium and has placed a consistent effort on annotating genes with GO biological process and molecular function terms, as well as placing gene function in the context of a cell component when warranted.  These GO assignments together with the rest of the curation efforts and services WormBase provides, put C. elegans research in a larger biological scope for the understanding of biological processes and create a ready means for our community to access it.

Cross species analysis is also supported by WormBase. Currently, WormBase contains the completed genomic sequence of C. elegans and has recently added  five genomes of related sister species, bringing the total to ten nematode genomes (five sister Caenorhabditis and five distantly related nematode genomes).  The C. elegans genome can be viewed and navigated using the latest GBrowse genome viewer developed by Lincoln Stein.  This genome viewer allows direct comparisons between C. elegans predicted gene structures to  some of these different species in its synteny viewer.

What if your model system of choice isn’t C. elegans? First, don’t despair; it’s never too late to switch organisms. We jest. Still, WormBase has great utility for users working in other model systems. First, you can bring the extensive experimental evidence available in C. elegans to bear on research problems outside of the system. For example, you can search WormBase using Uniprot identifiers to quickly identify orthologs. You can also navigate through the complete cell pedigree using an Anatomy Ontology browser, or explore neuronal connectivity of C. elegans through the direct links to NeuralNet.  Ontology browsers are also provided for GO terms and phenotypes, which should provide you with a wealth of information and context for your gene of interest.

Recently, WormBase celebrated its 10th anniversary, a heady milestone and veritable eternity in internet time. WormBase has come a long way from our initial days of housing mainly genomic data for a single nematode to now hosting pages upon pages of extracted biological descriptions of various aspects of those genes sequenced so long ago.  And now that we have many more genomes to deal with, the fun continues in a new direction to build a richer repository for scientists to use to uncover the mechanisms of development.

I’d also like to take this opportunity to point out related projects that may be of interest. As mentioned above, the Caenorhabditis Genetics Center houses, catalogs, and provides strains to the worm community.  Many knockout and allele generating consortiums are willing suppliers of strains with a lesion in your favorite worm gene. These include the C. elegans Gene Knockout Consortium,  the National Bioresource Project of Japan, and  NemaGENETAG. WormAtlas along with  NeuralNet is another very important web resource that we link to for our community to get an  in-depth view of the anatomy and wiring of the worm.  And finally, WormBook,  a companion website to WormBase, is a peer-reviewed reference guide to the genetical analysis and experimental methods used for studying C. elegans, as well as providing copious chapters reviewing all aspects of the biology of C. elegans and related species.

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Making life out of noise: “Stochasticity in cell and developmental processes”. Cumberland Lodge, Windsor, UK, 17-20 October, 2010. Organized by The Company of Biologists.

Posted by , on 28 October 2010

I always travel with my suitcase packed with genes. Airports, planes and trains offer me the only instances where I find two hours solid of work, and they (genes) are then my best companions. However, in my discipline – developmental biology – it seems lately that, by simply analysing more genes, we are not getting closer to understanding how the information in the genome flows within cells as these multiply and form wonderfully complex organs and organisms. That is why this time I arrived in Cumberland Lodge with little luggage, but with plenty of room in the suitcase to be filled.

The workshop “Stochasticity in cell and developmental processes”, sponsored by The Company of Biologists, and organized and chaired by James Briscoe (NIMR, London) and Alfonso Martínez-Arias (University of Cambridge), revolved around an unsettling question: if the molecular mechanisms that underlie the function of cells (and thereby life) are intrinsically disordered and noisy, how then does development proceed in such a predictable and robust manner -i.e. it looks totally deterministic? The intense scientific sessions distilled two main messages to be taken home. First, at a cellular level, heterogeneity rules. Sometimes cells and organisms coach this heterogeneity through interactions to reduce noise and to generate coordinated patterns of activity or gene expression, for example, oscillatory behaviors. Some other times, though, it seems that this heterogeneity is actually used by the system, and therefore is built-in within the cells – either individually or collectively.

Second, we need to quantify. Not that cell and developmental biology have been totally disconnected from maths, but qualitative descriptions, often open for interpretation, have abounded. Numbers will take us from classical cellular and developmental biology to a frontier located at the intercept between biology and physics – a frontier that will rapidly blur. The intelligent combination of quantification, modeling and experimentation (the latter more powerful than ever) is already demystifying some of the biology concerning stem cell biology and organ growth. The science and the discussions that followed at this workshop gave the strong feeling that this new frontier in cell and developmental biology is within reach.

The organizers brought together a very interesting sampler of scientists along a (morphogenetic?) gradient of expertise – from the mostly experimental to the mostly theoretical – all of whom were already engaged in research at this frontier or, at least, thinking to move into it. A great mix.

In addition, the cocktail shaker could not have been better chosen. Cumberland Lodge is an elegant, old manor house surrounded by meadows, tall oak and chestnut tress and randomly passing pheasants, and it’s located in the middle of the Great Park of Windsor. Meals and coffee/tea breaks were held in wonderful rooms, with comfy couches, and decorated with old portraits, black and white photographs, and modern paintings. Just perfect for informal and productive chats. Dinner, and after dinner drinks, were especially productive (and who has ever doubted the exquisiteness of the English cuisine?!). The organizational support prior to and during the meeting, provided by Nicky Le Blond (The Company of Biologists), ensured that the meeting ran smoothly.

Now back to the lab. Genes, numbers, cells, functions, all wandering stochastically in my head. What a pleasure.

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Grant writing in Africa

Posted by , on 27 October 2010

Today I gave a grant writing seminar for about 25 participants and went through the general structure and preparation as well as the expectations of reviewers and granting agencies.  The whole presentation went really well, and I clearly had an interested audience actively taking notes and asking really insightful questions.  A good conversation followed about international collaborations and preliminary data. (How are you supposed to present preliminary data when you don’t have the resources or equipment to do some of the the first fundamental experiments?) One junior faculty member even gave me a grant he was about to submit to ask me for feedback and suggestions, and I think I can expect several more to follow.  So I felt overall quite useful in expressing that this is a learned skill that takes years to acquire, that it’s worth the investment, and that individuals shouldn’t get frustrated by failure and give up.  They seemed surprised by the rejection rate in the US.

Two things came out of these conversations that were particularly striking. One was a question – “Are there mechanisms built in that recognize when you have difficulty with an approach and spend too much of your money troubleshooting before things start to work?”  That’s something none of us really have to worry about.  Grants in the US are *huge* by comparison, and we can spend time trying different things without worrying about the funds running out too quickly. We can be at least a little bit innovative and risky day to day. Here, a grant that is $20,000 is quite good. But that money has to be wisely and carefully spent, and there isn’t much wiggle room for trial and error if things don’t go precisely according to plan. And science is hard – sometimes things that “should” work just don’t work. It was a really good question and one I wasn’t sure how to answer other than “lean on the experience of others to work out technical issues more quickly so you can move forward more efficiently” and I strongly advised them to implement multiple experimental approaches to a given question – something is bound to work.

The most animated conversation that came of the day was surprisingly focused on the budget.  I hadn’t planned to talk much about administrative specifics until I was in a conversation with a faculty member this morning who said that the university “takes” from the research money they receive.  She really didn’t like this. It’s something I had already heard a few times since I was here, and it suddenly occurred to me what they were talking about.  So I used a slide in my seminar to explain the way it works in the US and probably most other places – there are “direct costs” like salaries, equipment, supplies, etc and “indirect costs” that are the institutional overhead (space, administration, electricity, water, etc). The indirect costs at KU are about 15% of the total grant, but the communication between the administration and the researchers hasn’t clearly stated what that money is for and how researchers should budget accordingly.  One of the grants administrators (also a research faculty) was present, which was fabulous because the two of use seemed to work well together to clear up a lot of misconception and mistrust.  Win.

On a less serious note – it’s Culture Week!  This is fascinating.  One week each year, the campus of KU becomes a festive environment of multiculturalism.  They have performances each night from all over Africa, so we’re getting to feel like we’re traveling the whole continent in our very short stay. There were dancers, musicians, and martial artists from Nigeria, Tanzania, and more in addition to the students at KU.  Even salsa dancers! Here I was captivated by the students from the school for the blind dancing a traditional African dance in grass skirts when the announcer enthusiastically introduced the KU salsa dancers as “probably the only students on the campus who know how to do this dance.” Exotic is clearly a matter of perspective!

Speaking of exotic.  The editing of this blog post was interrupted by one of those spectacular “wow” moments that come fewer and fewer as one gets more and more traveled.  I was sitting in the balcony area at the university guest house when a young man came to introduce himself.  He’s from Rwanda and visiting with his  dance troupe for culture week.  After a long chat, the whole group of about 20 young folks invited me to join them and burst out in traditional songs and dances.  He explained to me that these are not what they did for the performance – those were costumed and choreographed.  These were part of the long history of Rwandan culture, as one called it their “pastoral poetry”.  I can’t even begin to describe the scene.  It was one of marvel and mystery that this is such a rich culture I was getting a fleeting peek into.  Something I’ve never experienced before and may never have the blessing again.

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Categories: Funding, News

Postdoc positions in developmental neurobiology

Posted by , on 27 October 2010

Closing Date: 15 March 2021

POSTDOC POSITIONS IN DEVELOPMENTAL NEUROBIOLOGY

The MRC Centre for Developmental Neurobiology in London (UK) is opening two 3-5 years post-doctoral fellowships to work in Prof. Corinne Houart’s team, investigating the cellular and molecular mechanisms controlling telencephalon regionalisation and regulation of forebrain complexity in zebrafish and mouse. The comparative studies will use molecular and cell biology, high-resolution imaging, in vivo cell manipulation and genetics.

The candidates need a PhD. degree and research experience in molecular biology, developmental neurobiology and genetics.

The salary starts at approximately £30.000 per annum exclusive of London Allowance.

For enquiries regarding the posts offered, please contact Corinne Houart – MRC Centre for Developmental Neurobiology, King’s College London, New Hunt’s House, Guy’s Campus, London SE1 1UL – corinne.houart@kcl.ac.uk.



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Categories: Jobs

PhD studentship available: Chemical systems biology in zebrafish

Posted by , on 27 October 2010

Closing Date: 15 March 2021

We are seeking applications from highly motivated candidates, with a physical sciences background, and an interest in biology, to carry out a PhD to establish zebrafish as a model organism for chemical systems biology with which to carry out high-throughput chemical biology screens.

The zebrafish is a well-established vertebrate model organism due to its amenability for genetic screens, and its fantastic qualities for live imaging. Embryonic zebrafish also represent an almost ideal system for the study of small molecule function in vivo, due to their small size, aquatic existence, availability in large numbers, and molecular, cellular and system level similarities to higher vertebrates including humans. As with genetic screens, it is possible to employ different small molecule screening strategies using zebrafish. One can perform phenotypic screens, whereby one first identifies an interesting phenotype caused by a small molecule, and subsequently identifies the biological target(s) of effective compounds. In so doing one can discover new mechanisms of small molecule function, and, importantly, also identify new roles for known and novel proteins during biological processes. One can also carry out reverse pathway engineering whereby one selects a known target protein (possibly a drugable target), rationally designs a chemical library likely to affect this target, finds high affinity binders or inhibitors in-vitro and then tests the ability of candidate chemicals to affect the target in vivo, after which its biological effects can be studied.

This PhD project would be part of an ongoing collaboration between Dr. David Lyons (CNR) and Prof. Manfred Auer (CMVM, DPM, CIR) and would benefit from a unique combination of expertise in model organism biology, screening methodologies, chemistry and biophysics. Dr. Lyons’s lab focuses on the genetic and cellular basis of nervous system formation in zebrafish, with extensive experience in zebrafish biology and screening regimes. Prof. Auer is a biophysical chemist, who has 20 years of experience in the development of drug discovery technologies.  Prof. Auer’s lab designed, established and runs a unique chemical biophysics platform for lead compound discovery and chemical target validation. They can produce large scale tagged or untagged one-bead one-compound libraries, which they test against drug targets in bead based, chip based, cellular and now model organism assays. Small molecule compound function will be investigated in the PhD project in zebrafish using a systems aporoach. The molecular basis of biological systems will be studied using optical and phenotypic zebrafish models screened against fluorescently labelled small molecule and peptidomimetic libraries. Combined with top of the line mass spectrometry and single molecule microspectroscopy we hope to identify and validate new target compound pairs in a systematic approach. The successful applicant will therefore join a unique interdisciplinary environment, with ambitious long-term goals to carry out rapid cost effective high throughput screening of small molecule function at a whole organism systems level.

The ideal candidate will have a first class honours undergraduate degree, or an MSc with distinction in a relevant subject. Due to the ambitious and broad ranging challenges of this project significant laboratory expertise (> 1year) in a relevant area such as chemistry, biochemistry, or biophysics is required.

Interested candidates should first send a Curriculum Vitae and statement of specific interest to Dr. Lyons (david.lyons@ed.ac.uk) and Prof. Auer (manfred.auer@ed.ac.uk) by December 1st to discuss their potential suitability for the position. Short listed candidates will then be invited to apply formally through the Centre for Neuroregeneration website before panel interview.

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