Model systems, including laboratory animals, microorganisms, and cell- and tissue-based systems, are central to the discovery and development of new and better drugs for the treatment of human disease. In the latest issue, Disease Models & Mechanisms(DMM) launches a Special Collection that illustrates the contribution of model systems to drug discovery and optimisation across multiple disease areas. This collection includes reviews, Editorials, interviews with leading scientists with a foot in both academia and industry, and original research articles reporting new and important insights into disease therapeutics.
The Special Collection Editorial provides a summary of the collection’s current contents, highlighting the impact of multiple model systems in moving new discoveries from the laboratory bench to the patients’ bedsides. The launch issue can be accessed in full here.
To read and sign up for updates on the full Collection, which also includes keydrug discovery research and review articles published earlier in DMM, go to the Collection page at http://dmm.biologists.org/cgi/collection/drugdiscovery
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The British Society for Developmental Biology (BSDB) has elected us as your student and postdoc reps. We now have the opportunity to give students and postdocs a voice in moving the BSDB forward.
Therefore, we are trying to gauge what you want to see included as part of the society and the meetings. We have lots of ideas and have created a short survey for students and postdocs who are BSDB members (LINK). Your feedback will be key to determine what will be worthwhile in pursuing.
As a thanks we are offering four kindles and two £30 Amazon vouchers as prizes. We’d be grateful if you could complete it by October 26th.
A vacancy for a postdoctoral research associate is available for 2 years from 1 Jan 2016 in the first instance. Axonal endoplasmic reticulum is a poorly characterised compartment that is probably ubiquitous in axons, may mediate local and long-distance communication, and probably underlies a number of neurodegenerative mechanisms.
We have developed ways to visualise axonal ER in Drosophila, and identified mutations affecting its organisation. We now wish to understand more of its mechanisms of formation, and its physiological role.
This week the Node will be in Portugal! We are first attending the joint meeting of the Portuguese, Spanish and British Developmental Societies, that is taking place in the Algarve. Let us know if you are attending as well, as we would love to meet you and hear your thoughts about the Node. If you are not attending, do check our twitter account. We will be tweeting from the meeting if the internet connection is good enough.
We are also making a scheduled stop in Lisbon. If you are in or around Oeiras on Monday the 12th of October, pop by the Institute Gulbenkian de Ciência at midday. Cat, our community manager, will give a talk about how to use social media to communicate your science (Ionians seminar room). We look forward to meeting you!
One of the main challenges of Developmental Biology is to understand the complex developmental mechanisms giving rise to different organs or whole organisms. In most cases, these involve the interplay between cell-cell signalling and cell and tissue movements driven by one or several cell behaviours (such as cell proliferation, cell migration, etc.). Cell signalling will affect how surrounding tissues grow or change in shape, which in turn will change the spatial context in which signalling is taking place. Such complexity in the developmental dynamics can account for the formation of quite complex organs, such as mammalian teeth1 or vertebrate limbs2, but understanding how perturbations on those developmental processes will affect the resulting phenotype is not trivial.
Multi-scale computational models can help in better understanding the dynamics of developmental processes both qualitatively and quantitatively. They should be built upon explicit mechanistic hypotheses about how development takes place. Computational models can then provide explicit quantitative predictions on how the morphology of the organ or embryo or the expression pattern of certain gene products change during development (Figure 1).
Figure 1. Model design and validation. Mathematical models need to be based on experimental observations. These are interpreted and a mechanistic hypothesis is formulated (i.e. how the system is supposed to work). The model is implemented by translating the hypothesis into a mathematical formulation and solved through computational methods. Model validation consists on testing how accurately the model can reproduce experimental observations. A validated model can then be used to predict the behaviour of the system under conditions that haven’t been yet reproduced experimentally.
In the Salazar-Ciudad lab we work on the design of computational models of development in order to study how the complexity of developmental dynamics may give rise to complex structures and how the presence of different types of developmental mechanisms in different lineages may affect their evolution. For some time we have been using a tooth development model1 in order to approach those questions. However, if one wants to tackle those questions from a more general point of view, organ-specific models of development are not enough. For that purpose we need a modelling framework that implements a general developmental toolkit, that is: 1) the ensemble of cell behaviours known to happen in animal development (cell growth, division, death, cell migration, adhesion, epithelial-mesenchymal transition, cell signalling and extracellular matrix modification), 2) the basic mechanical properties of epithelial and mesenchymal cells and extracellular matrix and 3) the freedom to design gene regulatory networks (GRN) that dynamically control the mechanical properties of cells and their behaviours. Such a modelling tool should be able to simulate the development of, say a tooth or a limb, given that we correctly choose the gene networks and initial conditions in each case. Most interestingly, this would allow to study in silico how to transform one organ into the other by replacing, for example, the tooth forming GRN by the limb forming GRN and vice versa. In a similar way evolutionary transitions between different organs or structures could be inferred by rewiring the GRN step-wise.
Although there already exist modelling frameworks of development3,4,5 none explicitly implements the differential mechanical properties of both epithelial and mesenchymal cells or the whole range of cell behaviours we enumerated above. Thus, we decided to develop the most general developmental modelling framework up to date with all the elements described above.
In a paper recently published in Bioinformatics we present this new modelling framework implemented in the open source software EmbryoMaker, freely available for download at our lab’s website. The software provides a graphical interface to visualize the progress of a simulation in real time. In addition, it comes with a user-friendly editing tools in order to design the spatial initial conditions of any developmental system made of either epithelia, mesenchyme and/or extracellular matrix (the size and shape of the tissues at time 0 and their mechanical properties and gene expression profiles) and the GRN (that is defining the number of genes that will participate, their regulatory interactions and their regulation of different cell behaviours). The editing tools can be further used during the simulation of development in order to manipulate the system in real time. For instance, groups of cells can be removed or replaced in the fashion of a graft experiment, or growth factor releasing beads can be placed in any point in the developing system (Figure 2A). Thus, EmbryoMaker may work as an in silico wet lab that allows to predict the outcome of possible experiments on the system of study before carrying them out in vivo or in vitro (Figure 1).
We also show how the modelling framework is able generate complex morphologies from rather simple initial conditions by combining different cell behaviours in a dynamic way (Figure 2B). In this case, the joint action of localized cell contraction, cell polarization and polarized cell division drive the invagination of a spheric epithelium by epiboly.
Overall we expect this new modelling framework to contribute positively to the advance of the Developmental Biology and Evolution fields by providing powerful predictive tools to aid experimental design but also as a means to systematically study the capacity of Development to generate complex and disparate structures and how those might evolve.
Figure2. Examples of simulations performed with the EmbryoMaker software. A, Simulation of a growth factor releasing bead experiment. The first row shows a developmental sequence in which an epithelial bud (blue and purple) grows over a mesenchymal condensate (pink). The second row shows the same process, but in this case a growth factor releasing bead is placed at a certain time during the simulation. The diffusible growth factor will only reach the cells closest to the bead and will increases their proliferation rate, thus making the left side grow larger than the right side. B, Simulation of a complex developmental system by combining several cell behaviours on a hollow spheric epithelium. The contraction of a localized group of cells causes a shallow invagination of the epithelium. Meanwhile, a molecular gradient is being formed towards the invaginated region (colors depict the concentration of the molecule: yellow is high and blue is low), and cells across the embryo are instructed to proliferate in the direction of the gradient. The directional growth of the embryo pushes cells deeper into the embryo in a fashion reminiscent of the process of gastrulation by epiboly.
5- Delile J et al. (2013) Computational modeling and simulation of animal early embryogenesis with the MecaGen platform. In: Kriete A, Eils R editors. Computational Systems Biology, 2nd ed. Academic Press. Elsevier pp. 359-405
Are you interested in attending a meeting or course in a DMM-relevant field during 2015? Apply for one of our new travel grants, valid for travel before the end of the year.
Applicants will usually be PhD students and postdoctoral researchers at the beginning of their research careers, who will use the funding to support their travel to relevant scientific meetings. We also welcome applications from independent group leaders and PIs with no independent funding, seeking support to attend meetings, conferences, workshops, practical courses, PI laboratory management courses and courses to re-train.
Abcam is pleased to announce that our November calendar of free live webinars, presented by expert guest speakers, is now LIVE!
Register for a webinar (or three!) today and come prepared with your questions for the live Q&A session at the end of every webinar.
Can’t attend the live webinar? Not a problem! Register for the event today and simply look for an email from Abcam Events the day after the live webinar with the on-demand recording.
Developing Durable miRNA Biomarker Technologies for Microbial Carcinogenesis in Resource Poor Settings
– David wrote his recent paper in Disease Models & Mechanisms, where he developed two novel and complementary strains that facilitate genetic studies in the mouse.
Discussion:
– Are PhD internships a valuable exposure to careers outside academia or a harmful distraction from research? Share your thoughts in the latest question of the month!
– You may have presented posters and given talks about your research, but how about a rap? Check out this Rapstract on a paper using the direct differentiation of motor neurons from mouse ESCs as a tool to identify genes that direct phrenic neuron identity
– Two interviews featured on the Node this month: an interview with Didier Stainier and an interview with Philip Zegerman
Postdoctoral Research Associate in Developmental Biology
Closing date : 25/10/2015
Reference : LSX-07097
Employment type : Fixed term for 3 years (full time)
Salary : £30,434 to £37,394 per annum
Location : Takahashi lab, Faculty of Life Sciences, University of Manchester, UK
Our laboratory is looking for a highly motivated and skilful developmental biologist to work on a full-time Leverhulme Trust funded project. The overall aim of this project is to study vertebrate head development with particular interest in its evolutionary origin. Using the zebrafish (Danio rerio) model system, you will investigate the genomic cis-regulatory mechanisms of the genes controlling craniofacial development. In particular, you will integrate this in vivo experimental approach with evolutionary research using amphioxus – a marine invertebrate closely related to vertebrate ancestors – in collaboration with Professor Peter Holland at Oxford.
You should hold (or shortly expect to gain) a PhD in a relevant subject, along with a research background in developmental biology or related fields. Excellent laboratory skills are essential. You will be required to establish zebrafish transgenic lines and conduct real-time image analysis in this project. Previous experience with any of these techniques will be an advantage.
The post is available for up to 36 months in the first instance, with an expected appointment date of 1 December 2015.
To apply online for this vacancy, please go to the website (https://www.jobs.manchester.ac.uk/displayjob.aspx?jobid=10397) and click on the ‘Apply for job’ button below. This will lead you to the University’s Job Application System, where you can complete and submit the online application form. A full role specification can be obtained from the same website. The closing date for applications is midnight on Sunday 25 October 2015.
Informal enquiries can be made to Dr Tokiharu Takahashi.
Postdoctoral Research Scientist in Neuroscience : Oxford, United Kingdom
Salary: Grade 7: £30,434 – £37,394 p.a.
Stephen Goodwin’s lab, based at the Centre for Neural Circuits and Behaviour, are looking to appoint a postdoctoral research scientist to work on a project entitled “Genetic Dissection of Sexual Behaviour”.
Professor Goodwin and his group use Drosophila courtship behaviour to study how sex-specific neural circuitry and behaviours are established during development by the action of complex networks of genes. The aim of the study is to understand how activity in functioning dimorphic neural circuits gives rise to a different sex-specific behavioural repertoire in the male and female fly.
The successful applicant will have a PhD in neuroscience, and experience with the study of behaviour would be desirable. Candidates must have an emerging publication record and a proven ability to communicate their work. Good organisational skills and a willingness to work as part of a team are essential.
The post is fixed-term and Wellcome Trust funded for 3 years and is based at the Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, Mansfield Road, Oxford, OX1 3SR.
The closing date for applications is 12.00 noon on 2 November 2015.
Please send a CV, letter of motivation, and at least two letters of recommendation to Prof Stephen Goodwin (stephen.goodwin@cncb.ox.ac.uk).
Model systems, including laboratory animals, microorganisms, and cell- and tissue-based systems, are central to the discovery and development of new and better drugs for the treatment of human disease. In the latest issue, Disease Models & Mechanisms (DMM) launches a Special Collection that illustrates the contribution of model systems to drug discovery and optimisation across multiple disease areas. This collection includes reviews, Editorials, interviews with leading scientists with a foot in both academia and industry, and original research articles reporting new and important insights into disease therapeutics.
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