Mitotic cell mechanics in a tissue context
Lead Research Organisation:
University College London
Department Name: MRC Laboratory of Molecular Cell Biology
Abstract
Both symmetric and asymmetric cell divisions require a complex set of molecular processes to ensure the proper orientation of the microtubule-based spindle with respect to cortical cues. In asymmetric divisions, cells first establish an axis of polarity in response to internal or external cues. This is then read by astral microtubules to orient the spindle to segregate cell fate determinants asymmetrically in the two daughter cells. In symmetric divisions, the spindle typically reads apical-basal polarity cues and mitotic cell shape in order to align in such a way as to divide to release tissue strain. In both cases, spindle orientation is likely to be important for high fidelity chromosome segregation. Understanding the role of mechanics in mitosis is therefore a fundamental problem in cell biology. In addition, it is currently thought that controlled ratio of symmetric versus asymmetric cell division plays a critical role in stem cell homeostasis, a phenomenon thought to be misregulated in cancer.
While much progress has been made in identifying biochemical signalling pathways that regulate cell division in general, little is known about the mechanisms by which normal epithelial cells and stem cells sense, respond to and resist forces. Only recently the role of force has been studied in spindle orientation of individual adherent cells, and mechanical stress is known to be a major external signal involved in epithelial cell regulation. Our preliminary data now show that forces also play a significant role in spindle orientation in tissues. Building on this work we plan to test how spindle orientation responds to external force during symmetric and asymmetric divisions and to identify the molecular machinery involved.
To do so we will explore the molecular and cellular mechanisms by which mitotic cells sense, respond to and resist mechanical forces using two complementary experimental systems developed in the Baum and Charras labs: i) a device that enables the mechanical perturbation of MDCK epithelial monolayers, and ii) the Drosophila notum, a tissue where genetics, mechanical perturbations and live imaging can be readily combined. In this way, we expect to identify conserved molecular mechanisms that ensure that cell division occurs with high fidelity in the context of an epithelium subject to
changes in mechanics. We will further test whether force also a play a role in asymmetric divisions (as a simple model of stem cell divisions).
We expect this work to have a significant impact on our understanding of fundamental questions in the fields of cell division, tissue homeostasis, stem cell biology and regenerative medicine. There are several lines of evidence that make clear the importance of bridging this gap in our understanding of the role of mechanics in cell division. First, passage through mitosis involves dramatic active changes in cell shape and cortical rigidity, which when perturbed may lead to cell division failure and chromosome mis-segregation; potentially contributing to cancer development. Second, the ability of a cell to divide and form a colony in a mechanically soft medium is a key test of cellular transformation and malignancy, implying a role for mechanics in cell division. Third, in cell culture the mitotic spindle typically aligns parallel to a substrate plane along the axis of greatest tensile force. Fourth, it is possible that symmetrical divisions which tend to increase the number of stem cells will be triggered by tensile stress. In this way tissues may respond directly to the need for more cells by increasing the number of cells via tensile-controlled proliferation combined to oriented cell division ensuring relieve of the tension across the tissue.
While much progress has been made in identifying biochemical signalling pathways that regulate cell division in general, little is known about the mechanisms by which normal epithelial cells and stem cells sense, respond to and resist forces. Only recently the role of force has been studied in spindle orientation of individual adherent cells, and mechanical stress is known to be a major external signal involved in epithelial cell regulation. Our preliminary data now show that forces also play a significant role in spindle orientation in tissues. Building on this work we plan to test how spindle orientation responds to external force during symmetric and asymmetric divisions and to identify the molecular machinery involved.
To do so we will explore the molecular and cellular mechanisms by which mitotic cells sense, respond to and resist mechanical forces using two complementary experimental systems developed in the Baum and Charras labs: i) a device that enables the mechanical perturbation of MDCK epithelial monolayers, and ii) the Drosophila notum, a tissue where genetics, mechanical perturbations and live imaging can be readily combined. In this way, we expect to identify conserved molecular mechanisms that ensure that cell division occurs with high fidelity in the context of an epithelium subject to
changes in mechanics. We will further test whether force also a play a role in asymmetric divisions (as a simple model of stem cell divisions).
We expect this work to have a significant impact on our understanding of fundamental questions in the fields of cell division, tissue homeostasis, stem cell biology and regenerative medicine. There are several lines of evidence that make clear the importance of bridging this gap in our understanding of the role of mechanics in cell division. First, passage through mitosis involves dramatic active changes in cell shape and cortical rigidity, which when perturbed may lead to cell division failure and chromosome mis-segregation; potentially contributing to cancer development. Second, the ability of a cell to divide and form a colony in a mechanically soft medium is a key test of cellular transformation and malignancy, implying a role for mechanics in cell division. Third, in cell culture the mitotic spindle typically aligns parallel to a substrate plane along the axis of greatest tensile force. Fourth, it is possible that symmetrical divisions which tend to increase the number of stem cells will be triggered by tensile stress. In this way tissues may respond directly to the need for more cells by increasing the number of cells via tensile-controlled proliferation combined to oriented cell division ensuring relieve of the tension across the tissue.
Technical Summary
The project aims at exploring the role of external forces in spindle orientation in epithelial mitotic cells in a tissue context. To address this question we will use a combination of methods using the fly notum and a device to apply tension on MDCK cells as complementary experimental systems.
MDCK monolayers can be grown for few hours under external force, fixed, immunostained and imaged for markers of spindle orientation in normal and perturbed conditions. Using this device we will reveal the role of applied tensile and compressive forces on spindle orientation. We will stain for key proteins involved in spindle orientation including NuMA, Dynein and E-Cad to get at the molecular processes involved and will then image these events live using the MDCK monolayers expressing tagged versions of NuMA/EB1. In parallel, we will use similar GFP-tagged markers to precisely correlate analogous changes in cell shape, spindle assembly and orientation in the fly notum. Importantly, in the fly we can use our understanding of force differences across the tissue together with laser ablation to determine the relative effects of force and cell shape on the pattern of cell division, which preliminary work shows can be separated.
Using both systems we expect to come to general about how forces (tension and compression) affect mitotic cell shape, spindle morphology, assembly, and orientation. To determine the molecules involved in force-dependent cell behaviour in fly and MDCK cells (sensitivity and robustness), we will begin with NuMA, which we showed polarises in response to tension prior to spindle alignment. Next we will test the involvement of potential upstream regulators (e.g. Galphai), the actomyosin cortex and of osmo-regulators identified in the RNAi screen carried out with the Piel lab.
Finally, we will test the role of force in asymmetric P1 divisions in the notum and on apical-basal oriented spindles in MDCK monolayers as a model for stem cell divisions.
MDCK monolayers can be grown for few hours under external force, fixed, immunostained and imaged for markers of spindle orientation in normal and perturbed conditions. Using this device we will reveal the role of applied tensile and compressive forces on spindle orientation. We will stain for key proteins involved in spindle orientation including NuMA, Dynein and E-Cad to get at the molecular processes involved and will then image these events live using the MDCK monolayers expressing tagged versions of NuMA/EB1. In parallel, we will use similar GFP-tagged markers to precisely correlate analogous changes in cell shape, spindle assembly and orientation in the fly notum. Importantly, in the fly we can use our understanding of force differences across the tissue together with laser ablation to determine the relative effects of force and cell shape on the pattern of cell division, which preliminary work shows can be separated.
Using both systems we expect to come to general about how forces (tension and compression) affect mitotic cell shape, spindle morphology, assembly, and orientation. To determine the molecules involved in force-dependent cell behaviour in fly and MDCK cells (sensitivity and robustness), we will begin with NuMA, which we showed polarises in response to tension prior to spindle alignment. Next we will test the involvement of potential upstream regulators (e.g. Galphai), the actomyosin cortex and of osmo-regulators identified in the RNAi screen carried out with the Piel lab.
Finally, we will test the role of force in asymmetric P1 divisions in the notum and on apical-basal oriented spindles in MDCK monolayers as a model for stem cell divisions.
Planned Impact
The main beneficiaries of this research are likely to be the scientific communities working on questions related to cell division, spindle orientation, cellular mechanics, epithelium homeostasis and stem cell biology. We also expect these data to have an impact in the field of cancer research, in relation to high fidelity cell division and the dysregulation of stem cells. This research also has the potential to contribute to nation health through its exploration of the fundamental biology underlying cell division in a tissue context, a process that is relevant to development, homeostasis, regeneration and disease. In the longer term this research may also be of relevance to tissue engineers, since there is a great interest in the role of mechanics in tissue growth. Through its potential impact on our understanding of stem cell biology and our development of tools for the application of force to entire tissues, this work is also likely to benefit the stem cell research community.
To ensure this work has an impact in these areas we aim to present our results, technological developments and new ideas at conferences that cover different relevant topics including cell division, role of force in tissue homeostasis, engineering, development, cell biology and at the BSCB (British Society for Cell Biology) and Cell Mechanics meetings and the ASCB. We also aim to publish the main biological findings in 2 papers in high impact journals. Where possible we will publish in open access journals. We expect the first of these papers to be submitted in 2014.
Through our involvement in HFSP, the EMBO YIP forum, EU and Weizmann-UK networks, we will ensure that this work reaches the global scientific community and leads to the development of new international research collaborations. Most significantly it will strengthen our collaboration with the Piel lab at the Curie Institute, another leader in the field.
Importantly, we will also make use of our MeDiCI network to make this work known to our commercial (Cytokinetics, Pharmatest; JPK; CYTOO and Cellastix) and clinical partners (G. Williams and O. Carpen). Moreover, in our discussions with them we will explore how best to ensure the exploitation and commercialisation of our research findings and tools.
Tools that will be developed through the project will be made available to the community. To ensure impact we will carry out workshops to train researchers in the novel methods refined during the course of this analysis. We expect this type of approach to make a contribution to the emerging field of cell and tissue mechanics, where such tools are sorely lacking.
A large number of graduate students will benefit from involvement in this interdisciplinary systems level research through rotation projects in the lab and through MRes and tutorial activities associated with these programmes. Similarly, undergraduates will be exposed to this work through internships and short projects. Short research training projects will be offered in 2013-15. Through this experience, we expect students to gain an understanding of the way productive interdisciplinary collaborations work.
We would hope to publicise the implications of our research by writing a review of the field in 2015 targeted to reach a general audience. In the long-term, this research is likely to have an impact on lifelong human health and well being. UK Plc will directly benefit from this high profile research as technological developments will be commercialised through UCL and will be made available to UK companies working in tissue engineering.
To ensure this work has an impact in these areas we aim to present our results, technological developments and new ideas at conferences that cover different relevant topics including cell division, role of force in tissue homeostasis, engineering, development, cell biology and at the BSCB (British Society for Cell Biology) and Cell Mechanics meetings and the ASCB. We also aim to publish the main biological findings in 2 papers in high impact journals. Where possible we will publish in open access journals. We expect the first of these papers to be submitted in 2014.
Through our involvement in HFSP, the EMBO YIP forum, EU and Weizmann-UK networks, we will ensure that this work reaches the global scientific community and leads to the development of new international research collaborations. Most significantly it will strengthen our collaboration with the Piel lab at the Curie Institute, another leader in the field.
Importantly, we will also make use of our MeDiCI network to make this work known to our commercial (Cytokinetics, Pharmatest; JPK; CYTOO and Cellastix) and clinical partners (G. Williams and O. Carpen). Moreover, in our discussions with them we will explore how best to ensure the exploitation and commercialisation of our research findings and tools.
Tools that will be developed through the project will be made available to the community. To ensure impact we will carry out workshops to train researchers in the novel methods refined during the course of this analysis. We expect this type of approach to make a contribution to the emerging field of cell and tissue mechanics, where such tools are sorely lacking.
A large number of graduate students will benefit from involvement in this interdisciplinary systems level research through rotation projects in the lab and through MRes and tutorial activities associated with these programmes. Similarly, undergraduates will be exposed to this work through internships and short projects. Short research training projects will be offered in 2013-15. Through this experience, we expect students to gain an understanding of the way productive interdisciplinary collaborations work.
We would hope to publicise the implications of our research by writing a review of the field in 2015 targeted to reach a general audience. In the long-term, this research is likely to have an impact on lifelong human health and well being. UK Plc will directly benefit from this high profile research as technological developments will be commercialised through UCL and will be made available to UK companies working in tissue engineering.
Organisations
- University College London (Lead Research Organisation)
- Francis Crick Institute (Collaboration)
- Institute for Bioengineering of Catalonia (Collaboration)
- University College London (Collaboration)
- Technical University of Dresden (Collaboration)
- German Cancer Research Center (Collaboration)
- Gustave-Roussy Institute (Collaboration)
- Curie Institute Paris (Institut Curie) (Collaboration)
- National Institutes of Health (NIH) (Collaboration)
- Pierre-Gilles de Gennes Institute for Microfluidics (Collaboration)
Publications
Rosendahl P
(2018)
Real-time fluorescence and deformability cytometry.
in Nature methods
Rosa A
(2015)
Ect2/Pbl acts via Rho and polarity proteins to direct the assembly of an isotropic actomyosin cortex upon mitotic entry.
in Developmental cell
Rosa A
(2015)
Ect2/Pbl acts via Rho and polarity proteins to direct the assembly of an isotropic actomyosin cortex upon mitotic entry.
in Developmental cell
Rodrigues NT
(2015)
Kinetochore-localized PP1-Sds22 couples chromosome segregation to polar relaxation.
in Nature
Rodrigues NT
(2015)
Kinetochore-localized PP1-Sds22 couples chromosome segregation to polar relaxation.
in Nature
Ramkumar N
(2016)
Coupling changes in cell shape to chromosome segregation.
in Nature reviews. Molecular cell biology
Ramkumar N
(2016)
Coupling changes in cell shape to chromosome segregation.
in Nature reviews. Molecular cell biology
Pulschen AA
(2020)
Live Imaging of a Hyperthermophilic Archaeon Reveals Distinct Roles for Two ESCRT-III Homologs in Ensuring a Robust and Symmetric Division.
in Current biology : CB
Description | We have shown how tissues relax following tension or compression over short timescales. We have shown how oriented divisions relax tissue stretch over longer timescales. We have written a review to make it clear that tissues are complex materials that respond to forces at different timescales in different ways. In addition, we have shown how Myosin regulates spindle positioning and alignment in the developing fly. This paper is under review. We are revising a paper that explains how spindles orient in cells that round via spindle-cortex signalling. We have shown that Notch-Delta signalling functions to regulate entry into mitosis. We have studied the influence of cell-cell junctions on mitotic rounding and division in primary human tumours and in MCF10A cultures. This work, carried out by Dr Helen Matthews with be the basis of her job proposals for a Group leader position in the UK. |
Exploitation Route | We are following up the cancer aspects of this work and the developmental control of asymmetric division as part of work funded by a CRUK programme grant. This work has got us interested in the evolution of cell division. |
Sectors | Agriculture Food and Drink Education Environment Healthcare Culture Heritage Museums and Collections Pharmaceuticals and Medical Biotechnology Other |
Description | I spoke during a debate on the ethics on the start of life with Baroness Deech. I also spoke to teachers as part of a Prince's Trust course - explaining about cell division. |
First Year Of Impact | 2015 |
Sector | Education,Healthcare,Government, Democracy and Justice |
Impact Types | Cultural Societal Economic |
Description | ASCB representative in Europe |
Geographic Reach | North America |
Policy Influence Type | Membership of a guideline committee |
Description | BSCB representative LMCB |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Description | A CRUK clinical studentship for Sushila Ganguli |
Amount | £100,000 (GBP) |
Funding ID | A23234 |
Organisation | Cancer Research UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2017 |
Description | Cancer Research UK programme grant |
Amount | £2,000,000 (GBP) |
Funding ID | 17343 |
Organisation | Cancer Research UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2015 |
End | 12/2020 |
Description | EMBO grant for Nunu Mchedlishvili |
Amount | € 100,000 (EUR) |
Organisation | European Molecular Biology Organisation |
Sector | Charity/Non Profit |
Country | Germany |
Start | 05/2015 |
End | 06/2016 |
Description | Hallmarks of skin cancer |
Amount | € 3,000,000 (EUR) |
Funding ID | RTG2099 |
Organisation | German Research Foundation |
Sector | Charity/Non Profit |
Country | Germany |
Start | 03/2015 |
Description | MRC infrastructure grant |
Amount | £3,571,652 (GBP) |
Funding ID | MR/M009033/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2015 |
End | 04/2018 |
Description | Marie Sklodowska-Curie Action Individual Fellowship (MSCA IF) |
Amount | € 100,000 (EUR) |
Funding ID | IEOCCD (840120) |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 04/2019 |
End | 05/2022 |
Description | Wellcome consortium grant to study the archaeal origins of the eukaryotic cytoskeleton |
Amount | £3,000,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 12/2016 |
End | 11/2021 |
Title | CRISPR/Cas9 edited cell lines |
Description | We have generated a library of knock in lines that carry mNeon tagged proteins that have different localisations. |
Type Of Material | Cell line |
Year Produced | 2018 |
Provided To Others? | No |
Impact | We have trained people at the LMCB in the methods and have discussed sharing resources generated with collaborative partners. |
Title | Microfabrication |
Description | Expertise in microfabrication gleaned from work in Paris (IPGG and Curie) |
Type Of Material | Technology assay or reagent |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | We have established a Making community through an annual workshop and a Making lab at the CRICK |
Title | New cell models /CRISPR consortium |
Description | We are putting together a consortium to generate new cell models. |
Type Of Material | Cell line |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | Its underway |
Title | Tools for cell confinement |
Description | Micro-fabricated devices for confining and patterning cells |
Type Of Material | Technology assay or reagent |
Year Produced | 2017 |
Provided To Others? | No |
Impact | We expect these methods to be broadly useful to study cell shape and mechanics |
Description | Biological Making Lab |
Organisation | Francis Crick Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have established a Biological Making Lab at the CRICK. This follows the model of the UCL Institute of Making and will be a creative space in which researchers from across the CRICK can use microfabrication technology to advance their own research. |
Collaborator Contribution | The lab is up and running. It has three staff. In addition, we have a Satellite group at the CRICK. |
Impact | We have participated in lots of public engagement in the CRICK. Moreover, the team is rolling out microfabircation training to the entire CRICK. We have also run 3 Microfabrication workshops in London, attracting people from across London, the SE and Paris. |
Start Year | 2015 |
Description | Boutros lab |
Organisation | German Cancer Research Center |
Country | Germany |
Sector | Academic/University |
PI Contribution | Lucie Wolf joined the lab for several months as part of her PhD. We trained her. |
Collaborator Contribution | The Boutros lab is helping us to generate an RNAi library. |
Impact | None thus far. |
Start Year | 2015 |
Description | Fanny Jaulin |
Organisation | Gustave-Roussy Institute |
Country | France |
Sector | Academic/University |
PI Contribution | I worked with Fanny Jaulin to study role of oncogenesis in mitotic cell rounding |
Collaborator Contribution | They provided access to material, microscopes etc, and paid for my accommodation and that of my staff (Sushila Ganguli and Helen Matthews). |
Impact | None yet |
Start Year | 2014 |
Description | Ginger - Giniger |
Organisation | National Institutes of Health (NIH) |
Country | United States |
Sector | Public |
PI Contribution | NIH Bethesda |
Collaborator Contribution | The Ginnier lab is hosting Ginger Hunter while she completes this work |
Impact | Paper in progress |
Start Year | 2015 |
Description | IPLS |
Organisation | University College London |
Department | Institute for the Physics of Living Systems |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have helped to set up IPLS. We have hired to Theorists who have joined UCL to work with researchers. |
Collaborator Contribution | I sit on the committee and helped to set it up - building upon UCL Systems Biology |
Impact | none yet |
Start Year | 2014 |
Description | Labex chair |
Organisation | Curie Institute Paris (Institut Curie) |
Country | France |
Sector | Academic/University |
PI Contribution | In 2013 and 2014 I was visiting CELTISPHYBIO Labex chair at the Institute Curie in Paris |
Collaborator Contribution | They provided me with desk space for 3 months in 2013 and 2014 |
Impact | collaborations with many teams at the Curie |
Start Year | 2013 |
Description | MDCK tissue stretch |
Organisation | University College London |
Department | London Centre for Nanotechnology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Stretching tissue with Guillaume Charras |
Collaborator Contribution | We are working together to test the impact of stretch on tissue mechanics and cell division |
Impact | several publications and devices |
Start Year | 2013 |
Description | Mammalian epithelial monolayers - Guillaume Charras |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Understanding of actin dynamics in epithelia |
Collaborator Contribution | Help with research direction |
Impact | in progress |
Start Year | 2011 |
Description | Microfabrication |
Organisation | Pierre-Gilles de Gennes Institute for Microfluidics |
Country | France |
Sector | Academic/University |
PI Contribution | In 2015 I visited the IPGG in Paris. We established a new collaboration between the UCL/CRICK Biological Making Lab and the IPGG. This builds on an ongoing collaboration between my lab and Matthieu Piel's lab. As part of this Matthieu Piel gave two seminars at our Microfabrciation workshop in 2015. |
Collaborator Contribution | They have agreed to pay for the 2017 meeting |
Impact | Building on this, we agreed to have an annual UK-French microfabrication meeting. In 2016 this will be held at UCL. In 2017 it will be held at the IPGG in Paris. We were able to sponsor the visits of PhD students and post-docs from Paris for the London event in 2015, and to bring our invited guest: Manuel Thery. During my visit to the IPGG, members of the GR helped me to generate microfluidic channels to grow tumoroids from patients in conditions of partial confinement. This aids live imaging and analysis, by making growth in 3D reproducible. In addition, the IPGG grey room manager helped advise on the requirements of a Biological Making Lab. This advice will be useful in the creation of the BML at the CRICK in 2016. |
Start Year | 2011 |
Description | Multidisciplinary CRUK Project Award application |
Organisation | University College London |
Department | Institute of Making |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Two post-docs Dr. Ravi Desai, UCL (Microfabrication) Dr. Helen Matthews, UCL (Cancer biology) have put together a team for a Multidisciplinary award. The grant is headed by myself and Prof. Mark Miodownik from UCL's Mechanical Engineering Dept and the Institute of Making. However, Helen Matthes and Ravi Desai (from Andy Oates lab) are leading the initiative. Dr. Alan Lowe, UCL (Imaging & quantification) Prof. Andrew Oates, UCL (Oscillatory signalling) Prof. Daniel Hochhauser, UCL (Clinical Research) |
Collaborator Contribution | We have pilot data |
Impact | none yet |
Start Year | 2015 |
Description | Screening for changes in cell mechanics with the Guck lab |
Organisation | Technical University of Dresden |
Department | Biotechnology Center |
Country | Germany |
Sector | Academic/University |
PI Contribution | We are carrying out the cell biology and RNAi screening. There is a post-doc in the Guck who began work in my team and is now spending 2016 in Dresden to optimise the setup for high throughput screens for genes that regulate mitotic cell mechanics. |
Collaborator Contribution | They are providing the technology to measure cell mechanics at high throughput Follow up work with be done in Paris with the Piel team |
Impact | Preliminary data suggests that the protocol works and can be used to identify mitotic cells and to study their mechanics in asynchronous populations of both human and fly cells in culture. The team have now combined 2 colour imaging with mechanical measurements, and has developed tools to image NEB live. |
Start Year | 2014 |
Description | Tissue stretching |
Organisation | University College London |
Department | MRC Laboratory for Molecular Cell Biology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Stretching to determine how physical force impacts cell behaviour in the fly Yanlan Mao's lab |
Collaborator Contribution | She has been looking at the impact of tissue stretch on N signalling and cell division |
Impact | none |
Start Year | 2016 |
Description | Visiting Professor at the Gustave Cancer Research Institute |
Organisation | Gustave-Roussy Institute |
Country | France |
Sector | Academic/University |
PI Contribution | After I made enquiries and had attended the GR annual retreat in 2014, Eric Solary invited me to establish a longterm collaboration with the Gustave Roussy Institute. This is one of the best places in the world to work with surgeons and pathologists in the study of cancer. Through this collaboration, I spent nearly 3 months at the GR in Paris in the autumn of 2015. They paid for my accommodation. In addition, a student in the lab, Sushila Ganguli, a medical oncologist visited for several weeks, and Dr Helen Matthews a Cell biologist in my team visited for a few days during my stay. During my time at the GR I was encourage to interact with several of the cell biology teams that were recently recruited to the Institute. I was asked to help mentor them. As an example of this I helped Dr. Fanny Jaulin to rewrite a paper that had been rejected by NCB prior to review for Nature, where it is now under review, and helped with a paper by Dr. Olivier Gavet. |
Collaborator Contribution | The Jaulin lab gave me access to surgeons, pathologists, patients and patient material. In addition, they provided me with access to tissue from PDX mice. |
Impact | During my stay at the GR, I performed experiments with members of the Jaulin team as part of a joint collaborative study of the cell biology of CRC epithelial tumours. This included studying the cell biology of tumours taken directly from patients receiving treatment at the GR. I optimised a protocol for carrying out long term fluorescent live-imaging cells from this metastatic tissue. While this proved challenging, we developed a protocol (using a number of cell permeable dyes and lentiviral infection of GFP-constructs) that is now relatively reliable, and can be used for further analysis. Remarkably, these metastatic cancers are epithelial and invade without undergoing EMT. This represents a great model in which to determine how epithelial mechanics influence cell division. During this period, I also developed a protocol enabling tissue isolated from PDX mouse models of CRC epithelial tumours to be passaged in vitro, without losing its cell biological characteristics. |
Start Year | 2014 |
Description | Xavier Trepat |
Organisation | Institute for Bioengineering of Catalonia |
Country | Spain |
Sector | Private |
PI Contribution | A student from the Trepat, Marina Uroz, will be joining our lab in the summer when she has completed her PhD thesis to work on the abscission project. More specifically, we will combine our expertise and use traction force microscopy to study the forces in the cytokinetic bridge. |
Collaborator Contribution | We thus far have shared data and ideas. |
Impact | None as yet. |
Start Year | 2016 |
Description | Article in economist about research |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | enormous amounts of twitter feed enormous amounts of twitter feed. post-doc application |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.economist.com/news/science-and-technology/21630959-how-complex-cells-evolved-mystery-new-... |
Description | Beatson cancer meeting 2015 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Gave talk at Beatson cancer meeting |
Year(s) Of Engagement Activity | 2015 |
Description | CRUK-AACR Joint Conference on Engineering and Physical Sciences in Oncology 2019 - presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | spoke at cancer research meeting |
Year(s) Of Engagement Activity | 2019 |
Description | European Cytoskeletal Forum meeting 2017 - helsinki |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | spoke at cytoskeleton meeting |
Year(s) Of Engagement Activity | 2017 |
Description | Gurdon post-doc talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Gave a talk about mitosis and evolution |
Year(s) Of Engagement Activity | 2015 |
Description | Imperial college - maths and biology |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Gave a talk to mathematicians and physicists. |
Year(s) Of Engagement Activity | 2016 |
Description | Invited talk Workshop Vienna |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | lots of discussion with people new ideas to take forward |
Year(s) Of Engagement Activity | 2013 |
Description | Invited talk at EMBO meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Interest from Cell editor Idea for future directions |
Year(s) Of Engagement Activity | 2014 |
Description | Jacques Monod Conference on Actin and Microtubules in Roscoff |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Gave talk at meeting - which was a brilliant meeting |
Year(s) Of Engagement Activity | 2015 |
Description | Manchester talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Gave a talk in Manchester |
Year(s) Of Engagement Activity | 2015 |
Description | NCRI session organiser |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Organised session on cancer cell mechanics |
Year(s) Of Engagement Activity | 2017 |
Description | PLM10 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Co-organiser PLM10 |
Year(s) Of Engagement Activity | 2015 |
Description | Plenary talk at US fly meeting San Diego |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I gave a plenary talk on cell division in flies |
Year(s) Of Engagement Activity | 2018 |
Description | Profile in JCB |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | lots of nice feedback Post-doc applicants |
Year(s) Of Engagement Activity | 2014 |
Description | Spoke at workshop on cancer mechanics |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Mechanobiology workshop |
Year(s) Of Engagement Activity | 2019 |
Description | Talk Paris IBPS |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presented work to Institute as part of their seminar programme |
Year(s) Of Engagement Activity | 2018 |
Description | Talk at Cancer evolution meeting (Cancer Research UK Marshall Symposium 2017) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | To discuss how cancers evolve |
Year(s) Of Engagement Activity | 2017 |
Description | Talk at Edinburgh Wellcome cell biology centre |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Was invited seminar speaker |
Year(s) Of Engagement Activity | 2018 |
Description | Talk at the Genetics Department in Cambridge |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | I was invited by the post-docs |
Year(s) Of Engagement Activity | 2018 |
Description | Visit to MPI CBG Dresden |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Talk |
Year(s) Of Engagement Activity | 2016 |
Description | Warwick |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Gave a talk and met students and PIs |
Year(s) Of Engagement Activity | 2015 |
Description | helped run workshop in India (by remote) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Organised and spoke by remote (3 lectures) to international students on programme |
Year(s) Of Engagement Activity | 2019 |
URL | http://indico.ictp.it/event/8736/ |
Description | talk Pasteur Paris |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Talk at Pasteur on cancer cell division |
Year(s) Of Engagement Activity | 2020 |
Description | talk at CellMech2017 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | spoke at cell mech meeting |
Year(s) Of Engagement Activity | 2017 |