This interview, the 73rd in our series, was recently published in Development. 

Animal cytokinesis is driven by an actomyosin ring that assembles at the cell equator and constricts to physically separate the two daughters. Although myosin is known to be essential for cytokinesis in multiple systems, whether this requirement reflects its motor or actin crosslinking activities has recently been a matter of contention. A new paper in Development now addresses this problem using the first divisions of the Caenorhabditis elegans embryo as a model. We caught up with the paper’s three first authors Daniel Osório, Elaine Chan and Joana Saramago, and their supervisor Ana Carvalho, Principal Investigator at the University of Porto’s i3S consortium, to find out more about the story.

Ana, can you give us your scientific biography?

AC I graduated in biochemistry from the Faculty of Sciences of the University of Porto and did my doctoral studies on mitosis with Professor Bill Earnshaw at the Wellcome Trust Centre for Cell Biology in Edinburgh, UK. Then I moved to San Diego, USA, to do my postdoctoral work on cytokinesis in Professor Karen Oegema’s group at the Ludwig Institute for Cancer Research. In 2012, I moved to IBMC, the Institute for Molecular and Cell Biology in Porto, where I launched my independent research group. IBMC is currently part of the i3S, Institute for Research and Innovation in Health, a large consortium of three research institutes headed by the University of Porto.

Daniel, Elaine and Joana: how did you come to work in the Carvalho lab, and what drives your research today?

DO When I finished my PhD with Edgar Gomes in Paris working on the cell biology of nuclear positioning mediated by actin-binding proteins, I was looking to return to Portugal and my soon-to-be wife, having been away for almost 7 years. I found that the Carvalho lab had been recently established and had an opening in a C. elegans project to work with actomyosin and cytokinesis. In 2009 I had been one of the lucky ones selected for the physiology course of the Marine Biological Laboratory in Woods Hole, and during that course I got my first contact with C. elegans by interacting with the Oegema-Desai labs where Ana did her post-doc. Although we did not meet at the time I was very impressed by the model and its possibilities, so I guess the universe aligned later on and I was selected by Ana to take on this ambitious project.

EC In 2012, I got married to my Portuguese husband. After marriage, we decided to move from San Diego to Portugal, but at that time finding a research job in Portugal was not easy because of the economic crisis. But I did not give up my research dream. I contacted Ana because I really liked her research projects studying cell division in C. elegans, which was similar to my PhD background on bacterial cell division. After meeting her, we realised that we had both worked in the same university in San Diego before moving to Portugal, just in different buildings. We never had a chance to meet on the UCSD campus but we got our chance in Portugal! Ana and I have been working on actomyosin projects together for almost 7 years.

JS In 2013, I started my Master’s thesis and I knew that I wanted to do cell biology, and I started to search for an interesting lab. I visited a few labs, but when I saw a beautiful C. elegans embryo undergoing cytokinesis on Ana’s computer I knew that I had found what I was looking for. I also loved the idea of doing live microscopy, which was a dream of mine since I was a little girl: to see what our eyes can’t see. I liked it so much that I stayed to do my PhD after my Master’s.

Why has myosin’s precise role in cytokinesis been controversial?

DO Well, first and foremost because if you deplete or inactivate myosin, cytokinesis fails in most situations and systems. This only allows for the conclusion that myosin is required for the process, not that myosin motor activity is required. Second, I think it has been controversial because we tend to take the concept of conservation of processes too far: we want to assume that cytokinesis in a small yeast cell works exactly like it does in adhered cells or in a C. elegans embryo where divisions are so fast. Although the players and mechanisms are clearly conserved and a lot has been learned from studies in all systems from yeast to mammalian cells, we should accept that there may be system-specific variations. These should not be looked at as controversies, but may in fact reflect differences between the systems. Finally, the lack of good structural and quantitative information on the actomyosin organisation of the contractile ring in animal cells has limited the interpretation of phenotypes. Recent work using both electron and super-resolution microscopy are improving knowledge in the field.

Can you give us the key results of the paper in a paragraph?

DO, EC, JS & AC The motor activity of non-muscle myosin II is essential for cytokinesis and contractile ring contractility in C. elegans embryos, and the motor activity of muscle myosin II is required for contraction but dispensable for actin organisation in the body muscle of C. elegans adults.

Why do you think myosin motor mutants have a slower rate of contractile ring constriction?

DO Although several mechanisms may be involved, our work suggests that actin filament sliding through myosin motor activity is indeed important for constriction of the contractile ring. This is in agreement with previous proposals and with the organisation of the actomyosin network observed in recent electron microscopy and super-resolution studies. Therefore, mutants with reduced or absent motor activity have a reduced or absent ability to slide actin filaments, thus presenting a reduced rate of ring constriction.

When doing the research, did you have any particular result or eureka moment that has stuck with you?

DO I would not say eureka moments but there were some particular events that definitely contributed to the advance of the story. One was testing the effects of myosin mutations in the muscle. Although muscle and non-muscle myosins have biochemical differences and the muscle has a different organisation when compared to what we know about the contractile ring, we wanted an in vivo strategy that could help validate in vitro results as a complementary approach. Additionally, since we were not able to use animals expressing just the motor dead mutants (as they were sterile and did not produce embryos), the use of a wild-type copy from another location in the genome that could specifically be depleted by RNAi was a seemingly simple but very important step. Finally, getting the in vitro myosin motility assay to work was important. Although it has been established for many years, it is quite a challenging and meticulous process requiring several proteins to be expressed and purified in a functional form. This was quite time-consuming and not straightforward – in a sense I consider it a eureka moment for the lab because we started from scratch.

AC Being able to generate C. elegans in which the only source of UNC-54, the major muscle myosin, is UNC-54(R710C) and observing them moving normally was an important moment. Previous work has considered the equivalent mutation in non-muscle myosin II from mammalian cells to be ‘motor-dead’ based on an in vitro motility assay. As this residue and the region where it is located is highly conserved between muscle and non-muscle myosins of several organisms, we expected to obtain animals whose muscles were unable to contract and therefore were compromised in their movement. The result we obtained emphasised the fact that results from in vitro studies should be validated in vivo, where more complex scenarios exist.

And what about the flipside: any moments of frustration or despair?

DO Well, trying to analyse the specific role of any component of the cytokinetic contractile ring can be challenging. There is a quote from Ray Rappaport that explains it better than I can: ‘When I began working on cytokinesis, I thought I was tinkering with a beautifully made Swiss watch, but what I was really working on was an old Maine fishing boat engine: overbuilt, inefficient, never-failed and repaired by simple measures’. Additionally, myosin itself is quite a large and amazing motor and when tinkering with its gears it becomes complicated to decouple the effects on its motor versus actin-binding activities. All in all, everything involving myosin biochemistry was a challenge as we did not have any expertise.

So what next for you three after this paper?

DO I’m currently trying to capitalise on the multiple myosin strains we generated to study the interplay between muscle and non-muscle myosins in different C. elegans actomyosin-dependent contexts.

JS I am in the last year of my PhD and am currently trying to understand whether different types of myosin play a role during embryonic cytokinesis in C. elegans.

EC I am currently studying how the surrounding cortex influences the contractile ring and formin regulation throughout ring constriction.

Where will this work take the Carvalho lab?

AC There are still so many fascinating questions in the field and so studying the process of cytokinesis will continue to entertain us for a while. Our team is also moving onto exploring other cellular contexts involving actomyosin contractile networks in the powerful C. elegans system.

There are still so many fascinating questions in the field

What is the current situation for developmental and cell biology in Portugal?

AC Doing developmental and cell biology in Portugal is fun. Portugal is a beautiful and pleasant place to live, and more and more laboratories work in these fields. If only funding from the national Portuguese Foundation for Science and Technology would be more reliable and research positions more stable!

DO I think there are several very good cell and developmental biology labs in Portugal. The main challenge they face is funding and work position stability. The funding calls mostly centred on the Portuguese Foundation for Science and Technology have been quite erratic and there are very few alternatives for people trying to establish their labs in a more permanent way. Additionally, the amounts funded by national projects are not so high and this is quite an expensive field, so it is almost essential to secure funding from the European Research Council and other European sources, which are extremely competitive. As for work positions after PhD completion, the country is finally moving from a scholarship-based system to work contracts for post-docs and researchers. However, the university system is currently quite locked and most institutes, whether they are affiliated with the universities or not, have very limited possibilities to hire even the most talented PIs. This reduces my hopes that the country will succeed in maintaining and increasing the current level of its scientific community.

Finally, let’s move outside the lab – what do you like to do in your spare time in Porto?

DO Porto has become quite an amazing city over the years. There is now a whole new food, wine and craft beer scene that I love to explore while rediscovering some of the old classics. I like to walk and run around the river and seaside and when I have some free time I try to go up the river to the beautiful Douro valley where part of my family comes from. Those vineyards and amazing views bring back memories of my summer holidays as a kid. As I age, I grow more fond of them and I must confess I dream about having a vineyard of my own and producing my own wine!

EC In my spare time, I like doing different outdoor activities with my family – Porto has a wonderful beach for surfing and a large city park for my kid to ride a bike and play football.

JS I live near the beach and I like to go there and play with my beautiful baby girl. I also love to be surrounded by my friends, and we do a lot of dinners in each other’s houses.

AC Going for long walks by the beach is always reinvigorating, and going out for drinks and good food with friends is the best!

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Applications are invited for a postdoctoral fellow in the Brückner lab at The University of California San Francisco, Broad Center of Regeneration Medicine and Stem Cell Research.

The laboratory investigates inter-organ communication in innate immunity and hematopoiesis, focusing on the regulation of hematopoiesis by sensory inputs and signals from the nervous system, and molecular mechanisms of organismal immunity to bacterial infection (Makhijani et al. Nature Communications 2017; Sanchez Bosch et al. Developmental Cell 2019). The NIH funded project on organismal immunity will investigate a signaling relay between blood cells and the respiratory epithelia.

The ideal candidate is a talented and productive scientist with a background in developmental biology and genetics. Underrepresented minority candidates are in particular encouraged to apply. Prior work with Drosophila genetics, neurobiology or hematopoiesis/macrophage biology is desirable. General skills in molecular and cell biology, and good communication skills are expected. Candidates must hold a recent PhD, MD or MD/PhD degree, or anticipate such degree in the near future. We are looking for candidates who are motivated, hardworking, and have prior publications.

UCSF and the Broad Center offer a vibrant scientific environment and state of the art facilities. The Brückner lab provides infrastructure, a collegial environment, training and opportunities to work in teams.

Please send a CV, statement of research interests, and names and contact information of three references to:

Katja Brückner, Ph.D.
Associate Professor
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research
Department of Cell and Tissue Biology
University of California San Francisco
35 Medical Center Way, Room RMB 1026
San Francisco, CA 94143-0669
Tel +1 415 476 3827
Fax +1 415 476 9318
katja.brueckner@ucsf.edu
http://bruecknerlab.ucsf.edu/

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Virtual Fly Brain is a resource that helps Drosophila neuroscientists map and visualize neuronal circuits, and find the experimental reagents to manipulate the circuits to reveal their role in perception, learning, memory and complex behaviours. The successful applicant will aid this process in three ways: 1) by annotating the expression of Gal4 drivers within the adult brain, using data from large scale datasets and the primary research literature; 2) assisting in the integration of connectomics data and single-cell RNA sequencing datasets; and 3) leading the effort to assess the functionality of improvements to the website, by recruiting members of the local neuroscience community and working with them and other VFB members to perform usability testing of the website. Much of the curated data will also be integrated into FlyBase, the primary community resource for Drosophila genetic, genomic and functional data. 

Closing date: 14th February 2020

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Are you interested in the mechanisms that regulate organ development and prevent cancer formation?

We are looking for highly motivated and talented candidates to join our research team, lead by Dr. Zuzana Koledova.

We study processes, which govern mammary epithelial morphogenesis and homeostasis, and deregulation of which can lead to breast cancer. The main focus of the lab is on the role of mammary stromal cells in regulation of epithelial behaviour and the interplay of fibroblast growth factor signalling, cytokines and hormones in mammary gland morphogenesis and breast cancer. The approaches include advanced 3D organoid cultures of mouse and human primary tissue, genetic mouse models, state-of-the-art imaging techniques and mathematical modelling. The research group has extensive collaborations within the European Network of Breast Development and Cancer and beyond.

1. PhD position:

Anticipated start date:The position is available from September 2020 or upon agreement.

Requirements:

• MSc. degree from biology, biochemistry or its equivalent
• Interest in developmental and fundamental processes of life
• High motivation and work ethics, scientific curiosity and critical thinking, self-drive
• Interest in learning new methods, dexterity
• Willingness to travel abroad for research internship and conferences
• Tissue culture skills, imaging and/or mouse work experience are advantageous

We offer:

• Interdisciplinary project on highly relevant scientific topic
• Work in young, enthusiastic team with active international collaborations
• Participation at international meetings, internships at collaborating laboratories

To apply:

First contact the supervisor Dr. Koledova and send her your CV, motivation letter and a reference letter: koledova@med.muni.cz. Then apply at https://biology.med.muni.cz/doctoral-studies

The application deadline is 29^th February 2020.

2. Postdoc position:

Anticipated start date: The position is available from March/April 2020 or upon agreement but no later than by 30th November 2020.

The candidate should:

• be a researcher who has received a PhD or its equivalent within the last 7 years
• be a researcher who has worked at least two whole years in the last three years outside the territory of the Czech Republic in the field of research with a working time of at least 0.5 full-time equivalent, or who has been PhD student (or equivalent) abroad
• have a publishing record – in the last three years at least two publication outputs registered in the Thomson Reuters Web of Science, Scopus or ERIH PLUS databases and at the same time publications such as “articles”, “books”, “book chapters”, “letters” and “reviews”.
• be intellectually curious, self-driven and productive, have excellent communication skills, and enjoy working in a committed team
• have experience in the field of developmental or cell biology; experience in 3D cell culture techniques, live cell imaging and image analysis is highly desirable

The application should include:

• a CV including a summary of education and research experience, publication activity, involvement in research grants, etc.
• a scanned copy of the PhD diploma or an official letter certifying submission of a doctoral thesis for thesis defence and the planned defence date
• a motivation letter
• at least two reference letters

The application deadline is 29^th February 2020.

Please submit your application by e-mail to koledova@med.muni.cz and vrablikova@med.muni.cz

Informal enquiries are welcome at koledova@med.muni.cz

Further information on:

• Postdoc@MUNI: http://postdoc.muni.cz
• Koledova’s research group: https://www2.med.muni.cz/histology/zuzana-koledova/
• Masaryk University: https://www.muni.cz/en
• Brno: https://www.gotobrno.cz/en/

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Postdoc Position (NIH-funded):  Cell & Dev Biology of Neurons  –  How are Dendrites Shaped?
We seek a creative and productive individual who has a beginning or ongoing interest in neuron cell & dev biology. For initial studies, some familiarity with cell culture, immuno-precipitations/ running gels and microscopy would be a plus. The applicant should be finishing their PhD soon or have recently completed it. In this NIH-funded project we address the question: how are dendrite morphologies generated? The shaping of dendrites must take place properly for normal neuron connectivity to arise in the central nervous system, with alterations contributing to pathologies including mental retardation and dementia. Through the binding of novel protein-partners, we discovered that delta-catenin regulates the branching and length of dendrites. We propose to identify both the upstream pathways involved (e.g. ligands and kinases), and the downstream mediators (e.g. cytoskeletal modulators) that promote these dramatic branching versus lengthening outcomes. We will additionally examine related catenin proteins and their complexes. Laboratory members can select from a number of experimental systems including primary rat hippocampal neurons, mammalian cell lines, and frog embryos, plus undertake collaborative ventures involving other models. Pierre McCrea PhD (PI) has extensive mentorship experience. Prior trainees have gone on to successful academic as well as other rewarding scientific careers.

Environment.  The Texas Medical Center in Houston houses UT MDACC and multiple other top-flight scientific institutions within walking distance (Baylor College of Medicine; UT Health Science Center; Rice University; Methodist Research Institute; TX A&M Institute of Biosciences and Technology), or within bicycling distance (U Houston). This immense depth of collaborators/ programs/ cores insures a cutting-edge research/ ideas environment. Houston boasts a diverse culture near the Gulf Coast, and affordable living in our nation’s fourth largest city. MDACC offers well-regarded professional development opportunities and benefits. This is an NIH pay-scale position.

Please send:

• Cover letter or email stating your general career objectives and research interests
• NIH-Biosketch or CV
• Names of three references

Contact
Pierre McCrea PhD
pdmccrea@mdanderson.org

Department of Genetics, The University of Texas MD Anderson Cancer Center (UT MDACC)
Houston TX 77030

McCrea Lab Website

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PhD and Postdoc positions are available in the group “Cellular sex and physiology” in the Institute of Biology Valrose – Nice (France).

We are interested in developmental, metabolic or behavioural sex differences and aim to understand how sex chromosome constitution (XX versus XY) impacts physiology across the body. We are currently identifying new genes/pathways and concepts driving sex chromosome effects using multi-scale approaches combining biochemistry, genetics and cell biology. For this, we use the fruit fly Drosophila melanogaster as a model system (see Hudry et al., 2016 Nature and Hudry et al., 2019 Cell). More information can be found on the lab webpage (http://ibv.unice.fr/research-team/hudry/).

The positions will be funded through an ERC starting grant and would ideally start in  2020. We seek highly motivated candidates with interests in cell and developmental biology. Candidates should have a good working knowledge in live imaging and image analysis or prior experience conducting behavioural experiments. Previous experience with Drosophila is a plus, but is not mandatory. We strongly value team spirit and a positive work environment.

If you are interested, please contact Bruno Hudry (applicationhudry@gmail.com) with your CV and a brief statement of your research interests, key areas of expertise and up to 3 recommendation contacts.

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Interested in vascular development?

The Ruhrberg lab at UCL has 2 postdoc positions:

Post 1: https://www.jobs.ac.uk/job/BXT923/research-fellow

Post 2: https://www.jobs.ac.uk/job/BXV041/research-fellow

Post 1 requires experience in biochemistry, molecular and cell biology techniques as well as knowledge of transgenic and knockout mouse models to elucidate how NRP1 promotes brain vascularisation.

Post 2 requires experience in human embryonic stem cell culture and transcriptomics analyses to identify novel molecular and cellular markers for vascular progenitors in development and disease.

Post 2 will be co-supervised by Dr Paola Bonfanti at University College London’s GOS Institute of Child Health and the Francis Crick Institute.

Application deadline: 6th February 2020

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Position Title: Research Assistant or Research Associate

Position Summary: The Marine Biological Laboratory seeks a motivated, creative, and innovative Research Assistant or Research Associate to join the laboratories of Kristin Gribble and David Mark Welch in the Josephine Bay Paul Center for Comparative Molecular Biology and Evolution.  Our research combines comparative genomics, biochemistry, and life history to study aging, maternal effects, and DNA damage prevention and repair using rotifers, a novel aquatic invertebrate model system for studies of aging, neurobiology, genome evolution, and ecology.

The successful candidate will develop genome editing techniques in rotifers, including CRISPR/Cas9, as part of a broad initiative at the MBL to advance new aquatic and marine models for biological discovery.  Research will take place in the Bay Paul Center, with extensive DNA sequencing and bioinformatic resources, and in the NSF-funded Genome Editing Facility in the Marine Resources Center, where MBL scientists are developing new genetic and genomic tools for a wide range of marine invertebrates.  We invite individuals with experience in genome editing in other animals to join this expanding program.

Basic Qualifications:  Research Assistant applicants should have a B.A., B.S., or Master’s degree in biology, cell/molecular biology, biochemistry, or a related field.  Research Associate applicants should hold a Ph.D. or have commensurate laboratory experience.  This position requires proficiency and previous experience in molecular biology, microscopy, microinjection, and CRISPR/Cas9 methodology.  We are seeking an independent, organized, enthusiastic, and productive individual with robust problem solving skills. Excellent interpersonal skills, attention to detail, and a strong work ethic are essential. Position level and salary will depend upon education and experience.

Preferred Qualifications: The ideal candidate will have working familiarity with RNAi and transgenic protocols. Proficiency in bioinformatics is a plus. Previous experience in established animal model or in non-model systems is preferred.

Physical Requirements: Minimal exposure to biohazardous chemicals. Occasional lifting of heavy objects (<30 lbs).

Special Instructions:  Please apply on the MBL website and submit the following three items with your application:

(1) Cover letter describing your experience, research goals, specific interest in joining our group, and what you would contribute to the project
(2) CV/resume
(3) Contact information for 3-4 references (Please do not send letters at this time; we will contact references directly).

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PhD candidates on Quantitative Developmental Biology and Mathematical Modeling of Blood Vessel Growth near Tumors at Leiden University, The Netherlands

Key responsibilities 
The PhD projects will be part of an interdisciplinary project that will unravel how modifications of the extracellular matrix, as they can occur for example near tumors, can modify the structure of new blood vessel networks.

In this highly interdisciplinary project experimental biologists will work closely together with mathematical modelers on a daily basis. This approach enables the incremental development and testing of theories of single-cell behavior and collective cell behavior during tumor angiogenesis.

Based on cycles of iterative refinement of the mathematical model, followed by experimental validation, you will unravel aspects of blood vessel growth, and prepare your insights for publication in the biological, biophysical, and/or biomathematical literature. 

One mathematical modeling project will focus primarily on the cellular scale and on the molecular mechanisms of mechanical cell-cell interactions. The second mathematical modeling project will focus on collective cell behavior, initially simplifying the underlying molecular details. The experimental project will focus on imaging single cell behavior and collective cell behavior during angiogenesis.

Our interdisciplinary team carries out mathematical biology research in close interaction with our recently established experimental lab. More information about the group can be found here. This interdisciplinary group is embedded at the Mathematical Institute and the Institute of Biology Leiden, both at the Faculty of Science at Leiden University, and is physically based at, and embedded within the Cell Observatory of the Faculty of Science.

For more details about the positions and application procedure, see:

For the mathematical modeling positions: https://www.universiteitleiden.nl/vacatures/2019/q4/19-594-phd-candidates-on-the-mathematical-modeling-of-blood-vessel-growth-near-tumors

For the experimental position: https://www.universiteitleiden.nl/vacatures/2020/q1/20-018-phd-in-quantitative-cell-and-developmental-biology

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