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Postdoctoral positions in miRNA/siRNA biology in Lai Lab, Sloan-Kettering, NYC

Posted by , on 12 September 2017

Closing Date: 15 March 2021

We have openings for 2 motivated postdoctoral fellows with strong Drosophila molecular genetics experience and interest in integrative strategies to join our team.

Project 1. miRNA biology in the nervous system. Although miRNAs are often thought to mediate “fine-tuning”, we revealed many examples of profound defects in neural miRNA mutants (e.g. Garaulet J Neuroscience 2016, Sanfilippo Development 2016, Sun PLoS Genetics 2015, Garaulet Developmental Cell 2014). We uncovered other developmental and behavioral defects in neural miRNA mutants and utilize genetic, neurobiological and genome engineering strategies to precisely characterize their critical in vivo biologies.

Project 2. siRNA biology in the testis. What is endogenous RNAi utilized for? Surprisingly, there is still little clear biology. Building on our recent appreciation that Drosophila RNAi mediates adaptive gene regulation and productive spermatogenesis (e.g. Wen Molecular Cell 2015), we currently explore the evolution and function of RNAi systems across the Drosophilid phylogeny. We discovered networks of rapidly evolving RNAi substrates in the testis, and are using genomics and CRISPR/Cas9 in non-model fruitfly species to reveal critical roles of RNAi that cannot be seen in D. melanogaster, and may underlie speciation.

Funded positions with housing and medical benefits are available immediately. Please provide CV, motivation letter and references to Eric Lai, laie@mskcc.org.

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Embryosafari: an attempt at illustrating development

Posted by , on 12 September 2017

Hello, Community! In July, I revealed to the world my attempts at scientific illustration. Aidan (The Node’s Community Manager) took a keen interest in my work and was very kind to share it on social media. Here is my long-promised post about my biology art (which can be viewed at www.embryosafari.com).

Before I delve into the illustrations, let me introduce some background information about myself:

1st Instar (Science). Like many of us, I have been enthralled by biology since an early age. The specific focus of this fascination fluctuated through the years (from paleontology, through molecular virology to immunology), but I finally settled on developmental biology (in October 2006, to be precise), as I saw it was the science which tackled the most wonderful of all subjects: how bodies form (and evolve). Eventually, this lead to my PhD in developmental genetics in the labs of Anne-Gaelle Borycki and Phil Ingham, where I studied the expression of an ECM (extracellular matrix) gene using mouse, chicken and zebrafish embryos.

2nd Instar (Art). Similar to my fascination with science, I have enjoyed art (particularly clay modelling and pencil sketching) for as long as I can remember. As a child, I used to grab a block of clay and start sculpting (with arguable success) sci-fi creatures and characters that had grabbed my imagination on screen. Unlike science, I have never had any formal training in the arts (I don’t count art classes in primary school as such). In my later years, when I was already studying embryos, I frequently resorted to clay modelling when I needed to understand the three-dimensional anatomical organisation of a body region or organ. Subsequently, this “hobby” evolved into a digital form, the results of which I present below.

 

“Building The Brain”

 

This work represents the cytoarchitecture of the murine telencephalon at E10.5. The goal was to show the cell types at the beginning of neurogenesis. The fleshy (salmon) colour indicates the neuroepithelial cells (NECs) whose nuclei migrate “up and down” the thickness of the epithelium, undergoing INM (interkinetic nuclear migration). Mitoses occur close to the ventricle (the apical side of the epithelium), where the mitotic cells are indicated in orange-ish. What fascinates me is the fact that most NECs, even the mitotic ones, remain anchored to the pial basal lamina (the bright yellow plate on the top) via these long, thread-like basal processes. The first neurons in the telencephalon, those of the preplate, are indicated in red (Cajal-Retzius cells) and blue (prospective subplate neurons). Initially, this model was part of a bigger story which aimed to illustrate gyrification (cortical folding) in mammals, but it was too ambitious (one day I’ll go back to it!).

References:

http://dev.biologists.org/content/141/11/2182

http://emboj.embopress.org/content/23/11/2314

http://onlinelibrary.wiley.com/doi/10.1038/emboj.2008.227/abstract

https://link.springer.com/article/10.1007/BF00391127

 

“Cardiac Anatomy Of The Human Embryo”

Rarely there is a subject more irresistible than the embryology of our own species. Without any anthropocentric bias, human developmental anatomy is simply beautiful! Of all human embryology subjects, I consider brain, cardiac and craniofacial development most challenging in terms of morphological understanding. And because I enjoy such kind of challenges, I decided to tackle first cardiac anatomy, for which I knew the least. Ideally, I dream of creating illustrated plates for all Carnegie Stages, for both external and internal cardiac morphology, as well as for the major cellular and genetic events in cardiac development. Only time will show how feasible such an endeavour is. For now, I present illustrations on Carnegie Stages 9/10 and 12.

 

 

These plates illustrate the anterior half of the human embryo at a morphological stage between CS9 and CS10, viewed from different angles. This stage is interesting for it shows the fusion of the initially bilateral endocardial tubes (visible in Figure J on Plate I), and the presence of a distinct pericardial cavity (anterior coelom), shown in Figures C, D (Plate I) and in A-D (Plate IV). The abundant cardiac jelly, visible in Figure E (Plate I), and in Figures C and D (Plate IV), fills the space between the fusing endocardial tubes and the incipient myocardium. Importantly, myocardial progenitors in the second heart field add up to the growing myocardium (shown as blue arrows in Figure B on Plate IV). In addition to the heart, I spent some time sculpting the closing neural tube, the first two pairs of somites, the septum transversum, and the cranial neural crest (each cell was individually painted, as seen in Figure B on Plate I). For detailed examination, please view the images at full screen mode, or visit https://www.embryosafari.com/gallery.

 

 

This illustration represents the external morphology of the embryonic human heart at Carnegie Stage 12, viewed from different angles. The pericardial sac has been removed to expose the myocardium. The focus here is on the spatial relationship between the myocardium (salmon colour), the cardiac jelly (in yellow) and the vessels at the venous pole (blue). At this site, the second heart field continues supplying the myocardium with cardiomyocyte progenitors via the dorsal mesocardium (the cut edge in the top 3rd figure, left to right). The red colour indicates the vessels at the arterial pole of the heart, where the highly dynamic pharyngeal arch arteries form and regress in a quick, craniocaudal succession.

 

References:

http://circ.ahajournals.org/content/123/10/1125

http://circ.ahajournals.org/content/early/2010/08/09/CIRCULATIONAHA.110.953844.full

http://science.sciencemag.org/content/354/6315/aag0053.full

http://perspectivesinmedicine.cshlp.org/content/4/10/a015750.long

http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.35896/abstract

O’Rahilly R., Müller F., Human Embryology And Teratology, Third Edition,  2001

 

This is all about my work for now. If you wish to learn more, please jump to https://www.embryosafari.com/gallery

At the end, I would like to thank all curious, luminous and hardworking beings of science, without whom developmental biology wouldn’t have bloomed into its current state.

Thank you.

 

 

 

 

 

 

 

 

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Postdoctoral Fellowship in the Cell Biology of Tubulogenesis and its impact on Cell Differentiation

Posted by , on 12 September 2017

Closing Date: 15 March 2021

We are looking for a postdoctoral candidate with a strong developmental biology/cell signaling background and/or a biological image processing background to study the cellular and molecular mechanisms of lumenogenesis and tubulogenesis and their role in balancing cell proliferation and differentiation of multipotent progenitors in the developing pancreas.

Background:
The Novo Nordisk Foundation Center for Stem Cell Biology – DanStem has been established as a result of a series of international recruitments coupled with internationally recognized research groups focused on insulin producing beta cells and cancer research already located at the University of Copenhagen. DanStem addresses basic research questions in stem cell and developmental biology and has activities focused on the translation of promising basic research results into new strategies and targets for the development of new therapies for cancer and chronic diseases such as diabetes and liver failure. Find more information about the Center at http://danstem.ku.dk/.
Job Description: 
We are looking for a postdoctoral candidate with a strong developmental biology/cell signaling background and/or a biological image processing background to study the cellular and molecular mechanisms of lumenogenesis and tubulogenesis and their role in balancing cell proliferation and differentiation of multipotent progenitors in the developing pancreas. The candidate is expected to use both in vivo (mouse) and in vitro (human pluripotent stem cells) experimental models. The position is for 2 years with possible extension. The employment is planned to start December 1st 2017 or upon agreement with the chosen candidate.
 
Qualifications:
The candidate is required to hold a PhD degree in stem cell/developmental/cell biology/biological image processing. A few years of postdoctoral experience in the same areas is a merit. A candidate with biological background should also have hands on experience in mouse genetics, micro dissection of mouse embryonic organs, human pluripotent stem cell culture and differentiation, live-cell imaging, quantitative image analysis. A candidate with image processing background should have experience with segmentation and tracking in large 3D datasets and an interest in learning to work with the biological techniques described above. Finally, we are looking for applicants with a good record of peer reviewed scientific publications and grant writing skills.
Employment Conditions: 
The terms of employment are set according to the Agreement between the Ministry of Finance and The Danish Confederation of Professional Associations or other relevant professional organization. The position will be at the level of postdoctoral fellow and the basic salary according to seniority is 32.700-34.400 DKK/month. A supplement could be negotiated, dependent on the candidate´s experiences and qualifications. In addition a monthly contribution of 17.1% of the salary is paid into a pension fund. Applicants that are recruited from abroad may be eligible for a special researcher taxation scheme. In all cases, the ability to perform the job will be the primary consideration, and thus we encourage all – regardless of their personal background and status – to apply.
For further information contact Professor Henrik Semb, henrik.semb@sund.ku.dk
Foreign applicants may find the following links useful: www.ism.ku.dk (International Staff Mobility) and www.workingconditions.ku.dk.
Application Instruction: 
The application must be submitted in English, by clicking on “Apply online” below. Only online applications will be accepted. The closing date for applications is 23.59pm, November 1st 2017.
The application must include:
  • Cover letter detailing the basis on which the applicant scientific qualifications meet the requirements for this position.
  • Curriculum vitae.
  • List of references (full address, incl. email and phone number)
  • Diplomas – all relevant certificates.
  • List of publications.
Application procedure: 
After the expiry of the deadline for applications, the authorized recruitment manager selects applicants for assessment on the advice of the Appointments Committee. All applicants are then immediately notified whether their application has been passed for assessment by an expert assessment committee. Selected applicants are notified of the composition of the committee and each applicant has the opportunity to comment on his/her assessment. You may read about the recruitment process at http://employment.ku.dk. DanStem and The University of Copenhagen wish to reflect the diversity of society and welcome applications from all qualified candidates, regardless of personal background.
Apply online
Link for general info on the recruitment process: http://employment.ku.dk/faculty/recruitment-process
Founded in 1479, the University of Copenhagen is the oldest university in Denmark. With 37,000 students and 9,000 employees, it is among the largest universities in Scandinavia and one of the highest ranking in Europe. The University consists of six faculties, which cover Health and Medical Sciences, Humanities, Law, Science, Social Sciences and Theology.

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Postdoctoral Scientist in Quantitative Biology of Cell Fate and Tissue Dynamics

Posted by , on 8 September 2017

Closing Date: 15 March 2021

Grade 7: £31,604 – £38,833 p.a.

Applications are invited for the new position of Postdoctoral Scientist in Quantitative Biology of Cell Fate and Tissue Dynamics.

We seek a highly motivated, proactive individual who will benefit from the exceptional WIMM research environment and the recently purpose-built MRC WIMM Centre for Computational Biology, which brings together experts in analysis and modelling of large biomedical datasets. Working under the supervision of Dr Ed Morrissey, you will play a key role in developing mathematical and statistical methods to interpret intestinal stem cell data. You will work in collaboration with the experimental biology group of Dr Doug Winton, based at CRUK-Cambridge Institute. Your work will include developing analytical tools and resources to better understand stem cell dynamics within the intestinal tissue, both in healthy tissue and in the early stages of carcinogenesis.

You will have a PhD in a quantitative discipline (e.g. computational biology, physics, statistics, engineering or mathematics), with experience of working in a UNIX/LINUX environment.  You will be proficient in the use of at least one programming language e.g. c++, python, R or MATLAB. A prior publication record with evidence of key involvement in work and a strong interest in applying modelling to biological questions are also essential.

The position, available immediately, is funded by the Wellcome Trust and is fixed-term for 2 years.

Applications for this vacancy are to be made online. To apply for this role and for further details, including a job description and selection criteria, please click on the link below:-

https://www.recruit.ox.ac.uk/pls/hrisliverecruit/erq_jobspec_version_4.jobspec?p_id=130745

You will be required to upload a CV and supporting statement as part of your online application.

The closing date for this position is 12.00 midday on Friday 29th September 2017. Interviews will be held on Monday 16th October 2017.

Committed to equality and valuing diversity

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Internal mechanism found to be responsible for the limitless growth potential of epithelial tumours

Posted by , on 8 September 2017

Tumour (red) covered by collagen (green), which is being deposited by cells of the immune system (cyan). (Image: Mariana Muzzopappa, IRB Barcelona)

Researchers from the Development and Growth Control Laboratory at IRB Barcelona have identified the cell types and molecular mechanism responsible for the unlimited growth potential of epithelial tumours (carcinomas) and demonstrated that the growth of these tumours is independent of its microenvironment. “In epithelial tumours caused by chromosomal instability or loss of cell polarity, the interaction between two tumour cell populations drives malignant growth,” explains Marco Milán, ICREA Research Professor and head of the laboratory.

Published in the journal Proceedings of the National Academic of Sciences (PNAS) as a cover story of its 35 Issue, the study analyses solid tumours of epithelial origin in the fruit fly Drosophila melanogaster. “We have induced tumour development in two ways—by generating genomic instability and the loss of cell polarity. We have validated the causal relation between these two conditions—which are frequently observed in carcinomas—and the development of tumours,” explains Mariana Muzzopappa, first author of the study and postdoctoral fellow in the Development and Growth Control Lab.

 

Independent of the tumour microenvironment

To study the effect of the microenvironment on tumour development, the researchers examined tumour growth in the absence of adjacent cell populations, such as cells of the immune system or mesenchymal cells, which can act as a niche by supplying tumours with growth factors. The scientists observed that the tumour continued to grow in the absence of these two cell types.

Furthermore, they demonstrated that “the growth of epithelial tumours is dependent on activation of the JNK stress signalling pathway and that this pathway is intrinsically activated in the tumour, regardless of its microenvironment,” highlights Marco Milán.

Interactions between two tumour cell populations

The researchers have identified two functionally distinct cell populations within the tumour—one that proliferates and ones that does not—upon which internal growth mechanisms depend. “JNK is activated in a group of non-proliferating cells, namely those that show the highest degree of chromosomal instability or that have lost polarity. JNK triggers the expression of growth factors and makes those cells still in the epithelium to go on proliferating. The continued proliferation of these cells leads to an increase in chromosomal instability and the loss of epithelial polarity in the tumours. Consequently, the number of cells expressing growth factors rises. These cross-feeding interactions explain the unlimited growth potential of these epithelial tumours,” says Muzzopappa.

The mechanism of JNK activation differs depending on the tumour. “We have observed that tumours derived from chromosomal instability are induced by oxidative stress caused by ROS (reactive oxygen species), which triggers JNK. The mechanism in tumours that arise from the loss of cell polarity differs,” explains Marco Milán.

The results of this study shed further light on the causal relationship between chromosomal instability, loss of epithelial polarity and tumorigenesis and open new avenues for the search of therapeutic targets.

This study was supported by the Ministry of Economy, Industry and Competitiveness (MINECO) through ERDFs “A way to build Europe” and “la Caixa” Foundation PhD programme, that supports Lada Murcia PhD student.

Reference article:

Mariana Muzzopappa, Lada Murcia and Marco Milán

Feedback amplification loop drives malignant growth in epithelial tissues

PNAS (2017): doi: 10.1073/pnas.1701791114

 

VIDEO: OUR RELATIVE THE FLY

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Positions for Students (MSc and PhD) and Postdoctoral Research Fellows in Cardiovascular Genetics

Posted by , on 7 September 2017

Closing Date: 15 March 2021

Positions for Students (MSc and PhD) and Postdoctoral Research Fellows in Cardiovascular Genetics

Positions are available in the laboratory of Dr. Gregor Andelfinger at the CHU Sainte Justine Research Center, Montréal, Québec, Canada at MSc, PhD and postdoctoral level. Our work focuses on the genetic origins of cardiovascular diseases in the young and includes both genomics and functional approaches. In these projects, the successful candidates will apply genomic and molecular biology approaches to develop cell‐ and animal‐based disease models. Successful candidates will have a unique opportunity to do interdisciplinary research at all interfaces of developmental and translational medicine and publish their results in high impact journals.

We are looking for highly motivated and focused candidates who will work in collaboration with all other lab members. Team players with excellent communication skills who want to pursue a career in basic or translational cardiovascular research will be ideal candidates. We require expertise (post‐doctoral fellows) or willingness to learn (PhD and MSc students) a wide variety of basic and cutting‐edge techniques (histology, microscopy, developmental studies, Next Generation Sequencing including single cell, stem cell assays, CRISPR, and bioinformatics).

Applicants at MSc or PhD level must have excellent academic standing. Applicants for postdoctoral fellowships must have a recent Ph.D. degree and publications in life sciences, cell biology, or a related field.

The CHU Sainte Justine Research Center has recently moved into a brand‐new building and has all the required state‐of‐the‐art infrastructure and a dynamic international scientific community. Our Research Center is directly linked with Sainte Justine University Hospital Center, a very large tertiary pediatric center. The PI is affiliated with Université de Montréal, one of the largest universities in Canada and the largest francophone university in North America. Montreal is a vibrant bilingual city with a high quality of life. With a greater metropolitan area of 3.5 M, Montreal offers all scientific and cultural benefits of a large North American agglomeration with a European flair and beautiful surroundings.

Interested applicants are invited to provide the following documents to Dr. Gregor Andelfinger (gregor.andelfinger@recherche‐ste‐justine.qc.ca):

  • CV
  • Cover letter describing previous experience and career goals
  • Contact information for 3 references
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Bioinformatics position in a new informatics cluster supporting the Centers for Stem Cell Biology and Protein Research

Posted by , on 7 September 2017

Closing Date: 15 March 2021

 The position will provide bioinformatics support, develop new pipelines, and organize practical courses to help our scientists analyze and interpret their next-generation sequencing (NGS) data.
Bioinformatics position in the new informatics cluster supporting the Novo Nordisk Foundation Centers for Stem Cell Biology and Protein Research.
The position will provide bioinformatics support, develop new pipelines, and organize practical courses to help our scientists analyze and interpret their next-generation sequencing (NGS) data.
Bioinformatics position in the new informatics cluster supporting the Novo Nordisk Foundation Centers for Stem Cell Biology and Protein Research 
The NNF Centers for Protein Research (CPR) and Stem Cell Biology (DanStem) at Faculty of Health & Medical Sciences at the University of Copenhagen are establishing a new integrated informatics core that will cover a range of technologies.  This new core was recently expanded to include bioinformatics as a result of our establishing a new platform for single cell sequencing. We are currently looking for an ambitious bioinformatician who will assist with NGS analysis with in this core and provide new bioinformatics pipelines to individual scientists with in both centers.  The individual will be imbedded in a bioinformatics core with expertise that will include NGS, proteomics, and image data analysis.  The bioinformatician will join the centers starting from November 2017 or upon specific agreement.
DanStem was established as a result of a series of international recruitments coupled with internationally recognized research groups focused on insulin producing beta cells and cancer research already located at the University of Copenhagen. Current work in DanStem spans a broad range of stem cell and developmental biology and involves state of the art technologies including imaging and single cell NGS technologies.  DanStem currently hosts 12 research groups, which are working in wet lab and tissue culture laboratories that are equipped for working with both Embryonic Stem Cells (ESCs) and Induced Pluripotent Stem Cells (iPSC). Together with the Novo Nordisk Foundation Center for Protein Research DanStem is currently operating three scientific platforms: an Imaging facility, a flow cytometry platform and a sequencing facility. The platforms are staffed with experts and provide advanced training along with assistance in using the state-of-the art technologies. DanStem and the CPR recently collaborated to establish a single cell sequencing platform and the new informatics platform will build on the collaborative bridges initiated as a result of this new platform.
CPR has been established at the Faculty of Health and Medical Sciences, University of Copenhagen, to promote basic and applied discovery research on human proteins of medical relevance. The Center comprises a wide range of expertise and resources including proteomics, protein production, bioinformatics and general characterization of disease mechanisms. The Programme for Disease Systems Biology consists of the Big Data Management platform, which handles the data from other technology platforms, as well as two research groups that cover many systems-level aspects of biology and medicine, including the integration of molecular-level data and healthcare data, including biomedical texts.
Job description 
The job will sit at the nexus of the two centers and astride several existing joint efforts to bridge computational technologies including image analysis and single cell sequencing. The tasks associated with this position will include providing bioinformatics support to our scientists, constructing pipelines for their analyses, and running courses that will help them acquire bioinformatics literacy.  In particular this position will be responsible for developing and executing projects with other center scientists and helping them to make the best use of their own data and that already in the public domain.
Your profile
  •  Candidates must hold a Master and/or PhD degree in computational biology/bioinformatics or have similar relevant educational background and experience
  • Proficiency in at least one of the scripting languages (e.g. Python) is required
  • Sound statistic and fluent programming skills in R/Bioconductor is essential
  • At least two years of experience in the analysis of NGS data, particularly data related to gene expression and regulation
  • Knowledge of UNIX-like operating system
  • Experience in interdisciplinary collaborations or bioinformatics services will be an advantage
  • Scientific understanding of molecular biology and genomics is beneficial
  • Good English communication skills, both oral and written, are prerequisite for the successful candidate

 

We offer you

  • Stimulating, challenging and multifaceted research environment
  • Possibility for continued education and training
  • Attractive employment conditions
The employment has an initial duration until the end of 2020 with a possibility of extension. The employment is scheduled to start November 2017 or upon agreement with the chosen candidate. The place of work is at DanStem, University of Copenhagen, Blegdamsvej 3B, Copenhagen. Salary, pension and terms of employment are in accordance with the provisions of the collective agreement between the Danish Government and AC (the Danish Confederation of Professional Associations). In addition to the basic salary a monthly contribution to a pension fund is added (17.1% of the salary). Depending on qualifications, a supplement due to qualifications may be negotiated.
The application must include 
  •  Motivation letter
  • Curriculum vitae incl. education, experience, previous employments, language skills and other relevant skills
  • Copy of diplomas/degree certificate(s)
  • Three letters of reference
Questions 
For further information about the position, please contact
The University of Copenhagen wishes to reflect the diversity of society and welcomes applications from all qualified candidates regardless of personal background.
Only applications received in time and consisting of the above listed documents will be considered.
Applications and/or any material received after deadline will not be taken into consideration.
Application deadline: October 15th  2017 
Founded in 1479, the University of Copenhagen is the oldest university in Denmark. It is among the largest universities in Scandinavia and is one of the highest ranking in Europe. The University´s six faculties include Health and Medical Sciences, Humanities, Law, Science, Social Sciences and Theology www.ku.dk
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Graduate student positions

Posted by , on 6 September 2017

Closing Date: 15 March 2021

Our lab studies the early events of craniofacial development using teleost fish, zebrafish (Danio rerio) and Mexican tetra fish (Astyanax mexicanus) as model animals. We are particularly focused on evolution and development of the jaw structures. These include dentitions, sensory systems, and jaw bones. Formation of these structures involve complex interactions and we are interested in finding the molecular signaling pathways which regulate their development. This research addresses the questions related to the human congenital malformations and evolutionary development.

Applications are invited for fully funded studies which lead to the Master degree in Oral Biology in the area of molecular mechanisms of craniofacial development. Looking for a highly motivated student with good communication skills. Fine understanding of any of the following subjects would be highly beneficial: molecular biology, developmental biology and cell biology.

Our lab located at the Department of Oral Biology, College of Dentistry, University of Manitoba. The University is located in Winnipeg, the largest city in the province of Manitoba, Canada. The city has a rich cultural environment and the region provides exciting opportunities for outdoor exploration and recreation in all seasons
Please forward your complete CV with a brief statement of your research interest to Devi.Atukorallaya@umanitoba.ca

 

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Older wombs linked to complications in pregnant mice

Posted by , on 6 September 2017

This article is recent news from the Babraham Institute in Cambridge, view the original post here and the Nature Communications research paper here.

Credit: Ms Laura Woods. This is a fluorescent microscopy image of the womb of an elderly mouse. The bright green areas show cells which respond to pregnancy hormones. As a mouse ages, the womb becomes less sensitive to hormones, as shown by the uneven, patchy green. This is reflected in the developmental problems we see in the offspring from these older mothers.

Deciding to start a family later in life could be about more than just the age of your eggs. A new study in mice suggests the age of a mother’s womb may also have a part to play. This work, led by Dr Myriam Hemberger at the Babraham Institute and the Centre for Trophoblast Research in Cambridge, UK, is one of the first to look at the effects of age on womb health and it is expected to lead to new research into human pregnancies.

The risks of complications during pregnancy all increase with age. A woman in her late 30s is twice as likely as a younger woman to have a stillbirth, she is also 20% more prone to giving birth prematurely and more likely to experience conditions such as pre-eclampsia. Many of these effects have been linked to the deteriorating quality of ageing egg cells. Yet, this new research, published in Nature Communications, reveals that older wombs also have more trouble adapting to pregnancy.

By examining first pregnancies in aged mice, the team showed that, for mice as for humans, the risk of complications increases with age. Closer examination revealed that the wombs of older mothers are less able to support the growth of a placenta, meaning the developing young have poor blood supply, which slows their growth and can cause birth defects.

The co-first authors were Ms Laura Woods and Dr Vicente Perez-Garcia. Speaking about the findings, Ms Woods said: “We wanted to enhance our understanding of the increased risks of pregnancy in older mothers. When we compared mice who have their first litter in middle age to their younger counterparts, we found that the lining of the uterus does not respond as well to pregnancy hormones and this delays placenta formation. By identifying the key pathways affected by age in mice we have a better idea of what to look for in humans.”

Credit: Ms Laura Woods A fluorescent microscopy image of the womb of a young mouse for comparison. Note that the bright green areas are much more consistent.

Understanding the potential risks of pregnancy with age is an increasingly important issue. In the UK, more and more women are starting families later and in 2015, 53% of UK births were to women aged 30 or over. A 2016 report by the Human Fertilisation and Embryology Authority showed that freezing eggs for later use is also growing in popularity. In 2001, just 29 women opted for the treatment, rising to 816 by 2014.

Lead author, Dr Hemberger, Group Leader in Epigenetics at the Babraham Institute, said: “Overall, our study highlights the importance of the ageing uterine environment as a cause of reproductive decline in female mice. This is one of the first times that the considerable impact of age on pregnancy has been studied in detail beyond the effects of egg fitness. More research will be needed to establish if and how our results translate to humans.”

The shorter lifespan of mice means that they are useful for studying the effects of age on pregnancy but these results cannot always be directly applied to human pregnancies. These new results will help to guide long-term studies in humans but it is not yet clear what the implications of these findings will mean for family planning and human healthcare. It is clear that other factors besides egg quality may need to be considered when planning a family.

As a member of the Royal College of Obstetricians and Gynaecologists, Ashley Moffett, Professor of Reproductive Immunology at the University of Cambridge and expert on placenta formation, said: “We know that the so-called Great Obstetrical Syndromes, in particular pre-eclampsia are more common in older women but it’s still not clear why. Although more work is needed to demonstrate this effect in humans, this study could help advance research into these important questions”.

 

 

About the Babraham Institute:
The Babraham Institute receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) to undertake world-class life sciences research. Its goal is to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Research focuses on signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing.

Publication Reference
Woods L, Perez-Garcia V, Kieckbusch J, Wang X, DeMayo F, Colucci F, Hemberger M, (2017) ‘Decidualisation and placentation defects are a major cause of age-related reproductive decline. Nat Comms 8. http://dx.doi.org/10.1038/s41467-017-00308-x

Research Funding
This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC; Strategic Programme Grant BB/J004499/1), the Centre for Trophoblast Research, University of Cambridge, UK and a Medical Research Council (MRC) DTP studentship.

Animal Statement:
As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. Animals are only used in Babraham Institute research when their use is essential to address a specific scientific goal, which cannot be studied through other means. The main species used are laboratory strains of rodents, with limited numbers of other species. We do not house cats, dogs, horses or primates at the Babraham Research Campus for research purposes.

The use of animals in this study was performed in full compliance with UK Home Office regulations and with approval of the animal welfare committee (AWERB) at The Babraham Institute, and with the relevant project and personal licences. The study used the wild type C57BL/6 strain of mice housed at the Babraham Institute. Pregnancy was studied in mice between the ages of 8 and 12 weeks or 40 and 58 weeks. Embryo and placenta development were assessed around 11.5 days into pregnancy.

Please follow the link for further details of the Institute’s animal research and our animal welfare practices: http://www.babraham.ac.uk/about-us/animal-research

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2017 FASEB Mechanisms in Plant Development Meeting Summary

Posted by , on 5 September 2017

Written By: Margaret Frank, Ora Hazak, Samuel Leiboff, Heike Lindner, Concepcion Manzano, Lena Mueller, Michael Raissig, Annis Richardson, Adam Runions, Sebastian Soyk

 

A systems biology approach to understanding development

The 2017 FASEB meeting “Mechanisms in Plant Development” launched with a keynote by Philip Benfey (Duke University, USA) about the current understanding of root development. He presented an analysis of the dynamics of the SHORTROOT (SHR) – SCARECROW (SCR) – CyclinD6 (CYCD6) signaling network during root stem cell specification and the effects of specific carotenoid derivatives on lateral root prepatterning. Further, he proposed a minimal gene regulatory network consisting of epidermis-expressed SHR and MYB36 combined with CIF2 peptide treatment, which is sufficient for endodermis differentiation and Casparian Strip formation. Finally, he presented a new root phenotyping system for direct monitoring of maize root architecture in an agricultural field setting.

 

Next, Neelima Sinha (University of California, Davis, USA) discussed mechanisms of resistance to the parasitic plant dodder (Cuscuta spp.) in tomato. Using transcriptomics and whole genome resequencing in resistant and susceptible cultivars of tomato (S. lycopersicum), she mapped loci conferring resistance to dodder infection. Furthermore, she discussed the roles of lignin deposition in cortex cells for dodder resistance. She outlined a signaling cascade involving NBS-LRR proteins as well as MYB and AP2-type transcription factors that controls the expression of genes involved in lignin biosynthesis in response to dodder infection.

 

Finishing the first session, Anthony Bishopp (University of Nottingham, UK) presented mathematical approaches to explain vascular patterning in the root. His models suggest that vascular patterning can be established independent of initial asymmetry in auxin concentrations. Instead, a model solely based on spatial constraints and root growth are sufficient to enable vascular pattern in its final form to emerge from a simple genetic network, explaining the vast diversity seen in different flowering plants.

 

Alternations between generations 

The first session on Monday was under the theme Alternations between generations and started off with Thomas Dresselhaus (University of Regensburg, Germany) presenting fascinating work on a number of small signaling peptides that regulate pollen tube attraction and other aspects of fertilization in Arabidopsis and maize. He finished by presenting a recent transcriptome study regarding zygotic genome activation in developing maize embryos showing that 10% of genes are active a few hours after fertilization.

 

Next, Rita Groß-Hardt (University of Bremen, Germany) explained how the phytohormone ethylene regulates polytubey during pollen tube reception by triggering disintegration of the non-receptive synergid. In addition, she discussed the developmental consequences associated with the attraction of supernumerary pollen tubes.

 

The next speaker, Stewart Gillmor  (CINVESTAV, Mexico), discussed contrasting findings concerning the ratio of maternal and paternal transcripts during early embryo development. He highlighted his recent paper showing delayed paternal rescue of zygotic patterning mutants, and presented a new, comprehensive hybrid embryonic transcriptome suggesting a maternal gene expression bias in young Arabidopsis embryos.

 

Then, Duarte Figueiredo (Uppsala BioCenter, Sweden) highlighted the recently published work on the role of auxin in seed coat development. Auxin is produced in the endosperm and exported to the integuments in an AGL62-dependent manner, where it seems to repress Polycomb Complex genes and thus allows for seed coat formation.

 

Sharon Kessler (Purdue University, USA) presented recent work on the importance of the subcellular localization of MLO proteins during pollen tube reception. Additionally, she discussed ongoing work to understand the molecular basis of natural variation in fertility, resistance to powdery mildew, and ovule number.

 

Moritz Rövekamp (University of Zurich, Switzerland) unraveled the ancient function of the CrRLK1L family in cell elongation during vegetative development by studying the single family member MpFERONIA in the liverwort Marchantia polymorpha. He summarized preliminary results suggesting an additional role for MpFERONIA in sexual reproduction.

 

Finally, Siobhan Braybrook (The Sainsbury Laboratory, UK) discussed cell wall adaptations of brown algae to different tidal zones. She presented her studies on the re-hydration of artificial cell walls and embryo development in Fucus – and highlighted the importance of charged cell wall polysaccharides for marine plant survival.

 

Short Range Signaling

Developmental mechanisms are often regulated by release of signaling molecules or mechanical forces and perception of these signals by neighboring cells. The afternoon session of the meeting on Short Range Signaling was opened by Dolf Weijers (Wageningen University, the Netherlands) discussing new players in early embryo development. Weijers showed that polarly-localized SOK proteins influence the direction of cell divisions during early embryo development. In addition, using a whole-genome approach to determine the transcription patterns along the ontogeny axis of the root, his lab found that the main patterns are expressed in two opposing gradients. He proposed the idea that in the root meristem cells gradually switch from undifferentiated to differentiated cells.

 

Elizabeth Haswell (Washington University in Saint Louis, USA) introduced the role of mechanotransduction and mechanosensitive ion channels in development. In Arabidopsis ten genes encode proteins closely related to the canonical MscS mechanosensitive ion channel from E. coli. Haswell showed that one of these Arabidopsis genes, MSL8, protects pollen grains from the osmotic shocks intrinsic to their development and showed that it serves as a mechanoreceptor.​

 

The next speaker of this session, Joop Vermeer (University of Zurich, Switzerland) focused on cell volume control in endodermal cells overlying the emerging lateral root. He used live cell imaging to observe the cytoskeleton dynamics during lateral root growth through the endodermal cell layer. Vermeer showed that during this process microtubule arrays (visualized with MAP4) rapidly reorganise​ in the surrounding tissues and that a specific Arabidopsis MAP protein was induced in these cells.

 

Keiko Torii (University of Washington, USA) took us through the enigmas of receptor-ligand-based mechanisms defining stomata development.  Torii discussed the autocrine role of EPF1 peptide in the meristemoid cells as well as ERECTA-LIKE1 receptor distribution in different cell types and its correlation with cell-specific identity.

 

The next talk by Ora Hazak (University of Lausanne, Switzerland) was dedicated to the role of the first differentiating root vascular tissue called protophloem in sensing of CLE peptides. Protophloem is a dynamic continuously differentiating tissue providing the sugars and hormones necessary for the maintenance of the root meristem.  Her findings show that this tissue is responsible for the sensing of high levels of CLE peptides that results in locking of the protophloem in an undifferentiated state and later in the suppression of the root growth.

 

Nathanaël Prunet (Caltech, USA), presented the results of a collaborative work with Toshiro Ito and Frank Wellmer on the developmental origin of the phenotype of the Arabidopsis superman mutant, whose flowers show an increase in stamen number. Prunet nicely showed that flower patterning associates with auxin depletion and cytokinin accumulation at the boundaries between floral whorls and organs. He could demonstrate that this balance is inverted at the boundary between whorls 3 and 4 in the superman mutant. Prunet and collaborators showed that auxin biosynthetic genes are direct targets of SUPERMAN; they proposed that disinhibition of local auxin biosynthesis at the boundary between stamens and carpels is the cause of the superman phenotype.

 

Juan-Jose Ripoll (University of California, San Diego, USA) helped us to understand fruit growth processes. After fertilization fruit undergoes a dramatic increase in size that is essential to nourish and protect the growing seeds inside. Ripoll exploited Arabidopsis thaliana as a working platform and combined modeling, live imaging technologies and molecular genetics to follow the mechanisms that regulate fruit size and shape. ​

 

Antia Rodrigues-Villalon (ETH Zurich, Switzerland) closed the session with a discussion of the role of phosphoinositide homeostasis in vascular tissues development. During differentiation, vascular conductive cells fully (in xylem) or partially (in phloem) lose their organelles and cytoplasm to become conductive tissues. Rodrigues-Villalon showed that imbalance in phosphoinositide homeostasis at the plasma membrane suppresses differentiation both in xylem and phloem conductive cells by affecting vacuolar biogenesis.

 

Pluripotency and regeneration

Rüdiger Simon (University of Düsseldorf, Germany) opened the Pluripotency and regeneration session by discussing incoherent feedback loops active during the regulation of shoot apical meristem development in Arabidopsis. From genetic studies and fluorescence microscopy he identified previously uncharacterized members of the CLE peptide family that potentially restrict meristem size from the periphery of the CLAVATA3 domain.

 

Next, Michael Scanlon (Cornell University, USA) presented genetic and genomic analyses of maize leaf development. He showed the genetic dissection of the narrow sheath (ns) mutant, which results from mutations in two WOX3 transcription factor genes, NS1 and NS2. From RNA-seq and ChIP-seq experiments on laser microdissected shoot apices he concluded that NS1 is expressed in the pre-primordial margins and functions in recruiting the lateral domain of the maize leaf.

 

Agata Burian (University of Silesia, Poland) then proposed a microRNA-mediated signaling pathway that regulates axillary meristem development in Arabidopsis. Using live imaging she visualized miRNA expression patterns at the position of future axillary meristems that suggest roles of miRNAs in the timing of axillary meristem release.

 

Akira Iwase (RIKEN, Japan) started the second half of the session, with a discussion on wound-induced cellular reprogramming by the AP2/ERF transcription factor WOUND INDUCED DEDIFFERENTIATION 1 (WIND1). He presented ChIP-seq and RNA-seq experiments that identified direct WIND1 target genes, which may contribute to restoring pluripotency at sites of wounding.

 

Next, Ken Birnbaum (New York University, USA) talked about mechanisms of tissue reorganization during regeneration, using wounded Arabidopsis root tips as an experimental model. He used single-cell transcriptomics and time-lapse microscopy to show that patterning of the root stem cell niche is re-established across groups of cells rather than from a cryptic stem cell niche, and that this re-establishment of cellular organization is preceded by the rapid expression of MONOPTEROS (a root specification gene) independent of auxin.

 

Remko Offringa (Leiden University, the Netherlands) presented a molecular switch for rejuvenation and polycarpy in flowering plants that is regulated by members of the AT-HOOK MOTIF CONTAINING NUCLEAR LOCALIZED (AHL) protein family. He showed that enhanced AHL expression rejuvenates axillary meristems in the Arabidopsis inflorescence and allows Arabidopsis plants to flower and set seed multiple times. He concluded his talk with a discussion on the potential to exploit rejuvenation biology for increased crop productivity.

 

Laura Ragni (University of Tübingen, Germany) closed the session with a presentation about periderm development in the Arabidopsis hypocotyl and root. She discussed roles for Programmed Cell Death (PCD) and abscission during periderm establishment, and further presented data showing that periderm development is not affected when lateral root development is compromised.

 

Gene Regulatory Networks

From roots to fruits, the gene regulation and regulatory networks session showed how NGS technologies are addressing fundamental plant developmental questions in diverse plant species; including topics such as: (1) How roots cope with a “harsh world”, (2) How fruits decide which tissue develops into the flesh, (3) What defines fruit shape? (4) How the plant hormone, auxin does so much, and (5) Why different mutations in the same gene generate diverse phenotypes.

 

Siobhan Brady (University of California, Davis, USA) focused on how tomato roots develop the exodermis, a lignified and suberinised layer in the root. Using cell type specific sequencing technologies, they identified an evolutionary shift in cell-type specific expression, resulting in exodermis cells’ monopolizing suberin related genes. During drought these suberin genes are upregulated in commercial tomato varieties (Solanum lycopersicum), but not in the drought-tolerant wild tomato (Solanum pennelli), highlighting exodermis suberinization as a possible target for drought tolerance.

 

The “inside-out” fruit of strawberry was the focus of the talk by Zhongchi Liu (University of Maryland, USA). Strawberry fruit flesh develops from the inflorescence stem tip, leaving the maturing achenes, seed-containing ovaries, on the outside. Classical experiments demonstrated that strawberry fruit flesh development is regulated by auxin released by the seed-containing ovaries, but the molecular mechanism of communication between the seed and the maternal tissue was unclear. RNAseq and tissue specific auxin measurements, identified bidirectional communication involved in the specification of which tissue becomes the fruit flesh; the endosperm and seed coat produce auxin transported into the stem tip, and there is a novel role for FT in flesh to seed communication.

 

Next, Lars Ostergaard (John Innes Centre, UK) described how computational modelling and genetics explain the development of heart shaped fruits in Shepherds Purse (Capsella rubella) and the elongated fruits of Arabidopsis thaliana. The FRUITFULL (FUL) gene is required for growth during the post-germination phase and ful mutants have similar phenotypes in both species. They have also identified several additional fruit shape defective mutants by TILLING in Capsella such as heartless, heartbreak and braveheart.

 

Andrea Gallavotti (Rutgers University, USA) presented research on auxin-dependent transcriptional regulation in maize. Using DAP-seq and ATAC seq, they have identified binding sites for many Auxin Responsive Factors (ARFs), genome-wide. Many known activating and repressing ARFs bind upstream of the same genes (some 60% of ARF target genes), suggesting cooperative or competitive binding may generate auxin’s diverse effects.

 

Jeff Long (University of California, Los Angeles, USA) explored how different mutations in the same HD ZIP III transcription factors have diverse phenotypic effects in Arabidopsis. Using inducible expression, ChIPseq, and ChIP re-ChIP, they described complex regulatory interactions with transcription factor homo- and heterodimers with both, shared and unique binding sites upstream of important developmental genes, especially in the cytokinin pathway.

 

Capsella wild type and two fruitfull mutant alleles

 

A maturing fruit of the wild strawberry studied in the Zhongchi Liu lab

 

 

Patterning mechanisms

The session on Patterning mechanisms opened with a talk by Teva Vernoux (ENS de Lyon, France), who discussed the problem of robustly patterning organs at the periphery of the shoot apical meristem (SAM). Combining experiments and computational modeling he showed how spatial-temporal fluctuations in auxin signaling filters out noise to confer robustness on organogenesis, and highlighted a role for the CLAVATA3 domain boundary in the regulation of this process.

 

Next, Marcus Heisler (University of Sydney, Australia) discussed how phyllotactic patterning in the SAM is limited to the periphery of the meristem. He showed that organs are centered on a small gap between the expression domains of REVOLUTA and KANADI where auxin signaling is maximised, and highlighted how the configuration of this boundary region in the SAM cues both the placement of organs and their dorsoventrality. He also showed that wound-induced auxin depletion in the SAM rearranges the REV and KAN1 expression domains, leading to a new explanation for the influence of wounding on leaf dorsoventrality.

 

Continuing the theme of patterning boundaries, Annis Richardson (University of California, Berkeley, USA), explained how the understanding of boundary formation in grasses has been impeded by the dearth of mutants with organ boundary defects. She then presented fused leaf 1 (fsl1), a maize mutant with a range of phenotypes related to defective organ boundary formation and maintenance, and summarized work towards identification of the causal mutation in fsl1.

 

Next, Dominique Bergmann (Stanford University, USA) outlined an integrated picture of stomatal patterning and the establishment of polarities in these lineages. She presented recent work by postdoc Anne Vatén identifying a regulatory circuit involving cytokinin, several cytokinin-regulated CLE peptides and response regulators (A-ARRs), as well as the stomatal transcription factor SPEECHLESS, which provides a means to adaptively regulate stomatal lineages.

 

Expanding on the theme of tissue polarities Catherine Mansfield (John Innes Centre, UK) presented work investigating coordinated polarities in the leaf, focusing on BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL) a protein which polarly localizes to one edge of the cell during stomatal patterning. She showed that broad induction of BASL expression in a developing leaf has coordinated cellular polarities across the entire organ that appear to be independent of the stomatal lineage, consistent with the existence of an intrinsic tissue-wide polarity.

 

The talk of Aman Husbands (Cold Spring Harbor, USA) followed and returned to the topic of robustly patterning boundaries, focusing on Class III HD-ZIP (HD-ZIPIII) proteins and the role of the StAR-related transfer (START) domain these proteins contain. Using PHABULOSA as a representative protein for the family, he discussed work showing how the START domains – in complex with a so far unidentified ligand – confer switch-like behavior to HD-ZIPIII proteins while simultaneously increasing their transcriptional potency.

 

Finishing the session, Baoqing Ding (University of Connecticut, USA) discussed the molecular underpinnings of periodic pigment spot patterning in monkeyflowers (Mimulus) by reaction-diffusion. Mutant analysis and transgenic experiments show that these patterns are likely produced by diffusion and reaction of a compound activating anthocyanin formation (a R2R3-MYB activator) and a compound repressing the activator (a R3-MYB repressor), leading to the periodic activation of pigmentation.

 

Evolution and comparative development

All the investigators in this exciting session generated new molecular, genetic tools in diverse plant model systems to understand the development of complex, ever-evolving plant forms.

 

Miltos Tsiantis (Max-Planck Institute for Plant Breeding Research, Germany) studies leaf morphological diversity in Cardamine hirsuta, a relative of Arabidopsis thaliana with compound leaves. A computational model of leaf margin development with feedbacks between CUPSHAPED COTELYDON (CUC) transcription factors and the hormone auxin, suggested that changes in transport of auxin by PINFORMED (PIN) efflux carriers and the growth repressive activity of CUCs could generate diverse lobed and compound leaf shapes. Accordingly, the C. hirsuta REDUCED COMPLEXITY (RCO) gene encoding an HD-ZIP-I can reinforce local growth repression by CUCs thus creating compound leaves in C. hirsuta. RCO was lost in A. thaliana and when transformed back into this species it was sufficient to increase leaf complexity but not to cause complete Cardamine-like leaf development— although leaf physiology was altered indicating a potentially adaptive role. The latter was supported by finding positive selection signatures in RCO. Tsiantis suggested that few strong-effect regulators of leaf shape (like RCO) act with additional small effect genes to cause leaf margin diversity. He detailed efforts to isolate those and study their effects on growth

 

Elena Kramer’s talk (Harvard University, USA) explored the genetic basis of the petal spur, a unique floral structure in columbines. SEM of young petals showed that anisotropic growth contributes to the length of the final petal spur, with sustained cell elongation in Aquilegia species correlating with longer spurs. Transcriptomic profiling of developing petals, followed by inducible gene silencing by VIGS and in situ hybridization, show that division coordination by a TCP transcription factor is necessary for normal spur growth, and the function of STYLISH (SHI/STY) homologs is necessary for nectary development at the spur tip. QTL mapping of spur length in interspecies populations has identified a single mendelian locus that controls the presence and absence of spurs. Nonetheless, the genetic architecture of spur morphology may involve multiple loci, not shared between all columbine species.

 

Knowing that floral traits such as color, scent, and shape work together to attract pollinators, Cris Kuhlemeier (University of Bern, Switzerland) explored the genetics underlying the complex evolutionary history accompanying changes in pollinator preferences in petunia. QTL mapping of crosses between pollinator types (P. secreta, bee pollinated and P. exerta, bird pollinated) identified alleles of MYB transcription factor ANTHOCYANIN2 (AN2) as key to the evolution of bee pollination in P. secreta. Both species evolved from an ancestor carrying a pseudogene version of AN2 caused by a frame-shift deletion, leading to a white, hawkmoth-pollinated flower. However, in P. secreta, AN2 was ‘resurrected’ by an additional, codon-restoring deletion. Loci for UV floral display mapped to regulatory sequences of flavonol biosynthesis, together suggesting that somewhat simple molecular changes can underlie significant phenotypic and ecological niche changes.

 

Yoan Coudert (CNRS / Natural History Museum Paris, France) used the leafy shoot axis of the model bryophyte, Physcomitrella patens, to understand gametophytic branching. Unlike flowering plant sporophytes, where polar auxin transport and PIN genes are required to regulate lateral outgrowth, computational models of branch patterning in moss suggest that apolar auxin transport best explains observed architectures. Supporting this hypothesis, mutants in P. patens and manipulation of cell-cell diffusion rates show that the PIN auxin efflux carriers are minor contributors to architecture in P. patens, suggesting that not all plant architectures require polar auxin transport and alternative mechanisms exist in basal land plants.

 

Devin O’Connor (Sainsbury Laboratory, Cambridge University, UK) examined the function of closely-related PINFORMED (PIN) auxin efflux carriers in Brachypodium distachyon. Using fluorescent fusion proteins, Devin saw that Sister-of-PIN1 (SoPIN1), an efflux protein lost in Arabidopsis but conserved in most flowering plants, is expressed in the epidermis of the meristem and localizes asymmetrically towards auxin maxima. PIN1 paralogs BdPIN1a and BdPIN1b, however, express subepidermally in the developing vascular trace, transporting auxin away from lateral organs. Heterologous expression and complementation in Arabidopsis using the Brachypodium PINs showed that the SoPIN1 and PIN1 clades are not functionally equivalent. Loss of SoPIN1 in Brachypodium is sufficient to give a phenotype like PINFORMED1 in Arabidopsis, whereas PIN1 paralogs BdPIN1a and BdPIN1b together cause an internode elongation defect, suggesting that multiple auxin efflux carriers in Brachypodium may together perform the functions of Arabidopsis PIN1.

The RCO expression domainVirus-induced gene silencing (VIGS) in Cardamine hirsuta in the columbine flower (Aquilegia sp.)

 

 

Growth dependent morphogenesis

Adrienne Roeder (Cornell University, USA) launched the session by presenting a fluctuation-based patterning mechanism in Arabidopsis sepals (outermost floral organs). Sepals curvature is influenced by randomly patterned giant cells that form through endoreduplication. Giant cell formation requires the AtML1 transcription factor which has a linear, dosage-dependent role based on mutant and transgenic lines. Time-lapse imaging of YFP-AtML1 revealed that AtML1 expression fluctuates in sepal cells. Mathematical modelling of this, suggests that a specific threshold of AtML1 needs to be surpassed during the G2-phase of the cell cycle to allow endoreduplication and subsequent giant cell formation.

 

Ari Pekka Mahonen (University of Helsinki, Finland) presented elegant work describing how cambium stem cells are formed post-embryonically in the Arabidopsis root. Cell lineage tracing revealed that only pericycle and procambial cells in contact with xylem precursors contribute to the formation of cambium. Single cell lineage tracing and ablation experiments showed that the central cell layer acts as an “organizer” upon which the division capacity of adjacent cells depends. Conditional mutants also revealed a developmental module consisting of auxin, auxin response factors, HD-ZIP III transcription factors and WOX-like transcription factors required for radial cambium formation, secondary growth and correct patterning in the root.

 

Carolyn Rasmussen (University of California, Riverside, USA) presented a probabilistic mathematical model to predict 3D division plane orientation in plant cells. Time-lapse imaging of young maize leaves expressing a tubulin-marker line allowed for visualization of division plane (pre-prophase band) establishment and the division itself. The iterative model, seeking minimal division wall area and integration of preprophase band orientation predicts the correct transverse division 97% of the time in-silico (compared to 95% in-vivo), which is much closer to reality than previously published 2D models.

 

Pilar Cubas (Centro Nacional de Biotecnologia, Spain) presented work on identifying gene regulatory networks that regulate axillary bud dormancy. Both developmental and environmental cues can promote or inhibit bud outgrowth and are integrated by BRANCHED1 (BRC1), an inhibitor of bud growth. Transcriptomics analyses in repressed and activated buds in wild-type and brc1 plants identified three HD-ZIP I transcription factors, which together with BRC1 induce ABA biosynthesis in dormant buds triggering outgrowth. The triple mutant has a bushy phenotype when grown under shade conditions, which usually inhibit lateral growth and promote apical dominance.

 

Sebastian Soyk (CSHL, USA) presented recent work on the negative epistasis effects of MADS-box transcription factors on tomato yield. When stacking a trait that was selected during domestication and is linked to bigger fruit size with the “jointless” locus that facilitates mechanical harvesting, tomato inflorescences became highly branched and semi-sterile. Using a combination of natural alleles and CRISPR engineering, this can be overcome, resulting in a continuum of inflorescence branching, where some hybrid combinations produced single-branched inflorescences and significantly higher yields.

 

Hernan Lopez-Marin (Max-Planck Institute for Plant Breeding Research, Germany) reported on the identification of the super determinant (sde) mutant that fails to properly initiate axillary meristems in tomato. The SDE gene shows similarities to PRC1-like components but lacks the canonical RING domain. He proposes that a non-canonical PRC1 complex establishes competence for axillary meristem initiation.

 

Finally, Katy Guthrie (University of Missouri – Columbia, USA) presented work on the Suppressor of sessile spikelet 2 (Sos2) mutant, which suppresses the second spikelet formation specific to the maize clade of grasses. She showed that the Sos2 mutation seems to have roles in inflorescence, spikelet and flower meristems, and that the Sos2 mutation could partially suppress the indeterminate meristem mutation ramosa2.

 

Environmental Adaptations

The final session of the meeting on Environmental Adaptations kicked off with a talk by Stacy Harmer (University of California, Davis, USA), who introduced us to Sunflower as a model system for studying circadian rhythms. Before dawn, sunflower inflorescences re-orient themselves to face east in preparation for the rising sun. Harmer demonstrated that this ability to anticipate sunrise is dependent upon a spatio-temporal separation of auxin responses between day and night across the East and West halves of the sunflower stem. Notably, she was able to show that inflorescence orientation impacts temperature-dependent pollen shedding, which has a significant influence on the frequency of pollinator visits and yield.

 

The next talk was by Daniel Chitwood (Independent Researcher), who talked about a new method for measuring topology, called Persistent Homology, can be used to compare diverse 2-dimensional and 3-dimensional shapes. He presented several studies using persistent homology, including comparisons between roots and shoots, grape rachises from the core grape diversity collection in Geneva, NY, and a massive “leaf morphospace” that was generated from 182,707 leaves from different seed plant families. Surprisingly, he was able to show that there is predictive value to these measurements; 30% of the leaves in this massive leaf morphospace could be accurately assigned back to their respective plant families.

 

Next, Jessica Guseman (USDA-ARS Appalachian Fruit Research Station, USA) shed light on how environmental signals are integrated into the molecular control of shoot architecture in Arabidopsis and Prunus species. TAC1 and LAZY1 (members of the IGT gene family members) work together to influence branch angles. Guseman demonstrated that each of the IGT genes responds differently to light treatments and mutant combinations with core components of the light signaling pathway. Further work investigating how light influences the IGT family will help us to understand complex architecture problems in trees, for example – how understory branches respond to shading from the top of the tree.

 

Next, Ben Holt (Associate Professor at the University of Oklahoma, USA) took us through a rigorous series of experiments looking into the functional specificity for how the CONSTANS (CO) DNA binding complex regulates expression of the floral promoting factor FT. Using three-dimensional protein structures, chromatin modeling, and amino acid sequence alignments between the CO DNA binding complex and its functional analog, the Nuclear Factor-Y complex, Holt was able to pinpoint specific residues of the CO DNA binding domain that specify the enhancer element binding capacity of this complex.

 

Salehin Mohammad (University of California, San Diego, USA) spoke next on the connection between AUX/IAA signaling and glucosinolate biosynthesis. Mohammad used RNA-sequencing, glucosinolate profiling (with LC-MS), and genetic stacking, to delineate a signaling pathway that connects IAA5, IAA6, and IAA19 with the regulation of aliphatic glucosinolate biosynthesis. Surprisingly, he was able to demonstrate that mutants in this pathway are drought sensitive, suggesting a new role for aliphatic glucosinolates in abiotic stress tolerance.

 

The meeting concluded with an illuminating talk by Heike Lindner (The Carnegie Institute of Washington, USA) on the phenotyping capacity of GLO-Roots, a robotic system that uses a luciferase reporter system to track root architecture over time. Underground environmental pressures (for example water availability and nutrient composition) have the ability to shape root architecture over evolutionary time. Lindner is leveraging the geographic and genetic diversity of Arabidopsis to perform a GWAS for environmentally selected root architectural traits across a collection of ecotypes.

 

Conference attendance summary:

The 15th FASEB meeting “Mechanisms in Plant Development” 2017 took place once again at the Vermont Academy in Saxons River, VT. The organizers Prof. Doris Wagner (University of Pennsylvania), and Prof. Marja Timmermans (University of Tübingen) invited 26 speakers (including the keynote) representing the international “who is who” in plant developmental biology. With an almost equal ratio of 46% to 54% female and male speakers, respectively, this meeting represents an outstanding example for gender equality in science. One interesting fact, however, was that the vast majority of the invited female speakers were from US Universities (8 vs. 3 from Europe, 1 from Japan), whereas the vast majority of European invited speakers were male (9 vs. 3 from US, 1 from China/substituted by Australian). Unfortunately, 3 invited speakers could not attend the meeting and were substituted by equally qualified scientists. To promote visibility of early career researchers, 30 short talks were selected from submitted abstracts. 15 of those talks were given by PIs in pre-tenure stages of their career (7 female, 8 male), 3 by grad students (2 female, 1 male), and 12 by postdocs (4 female, 8 male, representing roughly the ratios of submitted abstracts). The outstanding program and the unrivaled reputation of this bi-annual meeting attracted 145 international attendees (54.5% male and 45.5% female) with 57.2% attendees coming from US Universities and research institutions, 32.6% from Europe, and the rest from other countries all over the world. Of the 119 attendees that disclosed their ethnic background, 12% were from underrepresented minorities (hispanic/latino, black/african american, native american/pacific island), 27% were asian, and 61% were caucasian.

 

One special feature of this conference is and has always been that speakers present a good amount of unpublished data to receive input and opinions from other experts in the field. In addition, all 145 attendees were invited to bring posters, and evening poster sessions in a relaxed environment gave the opportunity for very fruitful discussions and great interactions between young researchers and established PIs. An additional poster session was dedicated to grad students to promote visibility and guarantee interaction with more established scientists. Two “meet the speakers” lunches and the newly established “career development” lunch with topics as diverse as “how to publish your science” to “science and social responsibilities” encouraged interactions across different career stages. Overall, the friendly, enthusiastic, encouraging and inclusive environment of this conference is a shining example of how conferences should be and offers diverse role models for young scientists.

 

During the election of the organizers for the 2019 meeting, the community of plant developmental biologists once again proved how progressive it is, and voted Kenneth Birnbaum (New York University) and Jill Harrison (University of Bristol) as the next organizers. We are excited for the next FASEB meeting “Mechanisms in Plant Development” 2019 at St. Bonaventure University and we thank the Vermont Academy for being a great host of the past FASEB meetings.

 

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