The generation and evolution of biological form

Lead Research Organisation: MRC Laboratory of Molecular Biology

Abstract

Large organisms, like animals and plants, are made from enormous numbers of cells that work together. Under the microscope, one is struck by the extraordinary beauty and complexity of each individual “eukaryotic” cell in the collective. My team is fascinated by ability of these cells to rapidly reshape themselves to give rise to new structures, especially during division, as one cell becomes two.
We are also interested in the origins of complex cells. Remarkably, eukaryotes first arose over 1 billion years ago as the result of a merger between a relatively simple archaeal cell and a bacterial cell. While it is not known precisely how this happened, we recently proposed that eukaryotic cell architecture evolved in a step-wise manner, from the ‘inside-out”, as an archaeal host cell elaborated protrusions that it used to share resources with its free-living bacterial partner. If true, features once thought to be unique to eukaryotic cells may have their origins in archaea. This is a hypothesis we now aim to test.
Finally, by studying cell division in archaea and eukaryotes, we also expect this work to reveal new fundamental aspects of the cell division process that can be used to aid our understanding of human cancer.

Technical Summary

My lab is interested in the generation of biological form or “morphogenesis”. Our focus is on events at the cellular scale, because the cell is the unit of life and because even large-scale tissue movements are driven by changes in the shape and mechanical properties of individual cells.
The most extraordinary and fundamental of all morphogenetic events is cell division: the process by which one cell becomes two. During division, in the space of a few minutes, all the component parts of the cell must be moved apart and partitioned into two daughter cells. This must be done with precision, since errors are associated with diseases like cancer in humans, and frequently cause cell death.
Rapid changes in cell organisation, including those that accompany cell division, are brought about by a network of dynamic polymers - the cytoskeleton - which convert chemical energy into force. Strikingly, recent phylogenetic studies have has shown that the key cytoskeletal elements used to drive division and other shape changes in eukaryotic cells (actin, tubulin and ESCRT-III) are ancient proteins, which eukaryotes likely inherited from their archaeal ancestors. Taking advantage of this discovery, in exploring the fundamentals of the division process my lab is looking for similarities and differences in the mechanisms archaea and eukaryotic cells use to divide. Using eukaryotes and archaea (with a focus on Sulfolobus) as model systems, we aim to identify conserved processes, core principles, and to determine how division has changed during the transition from archaea to eukaryotes. We also expect this work to shed light on the process by which the eukaryotic cell first emerged from the symbiosis of an archaeal cell and its bacterial partner – something that remains one of the greatest mysteries in the history of life on earth.
Given the fundamental nature of cell division, we also expect this work to improve our understanding of the way the core division machinery functions to aid normal tissue development and homeostasis and, when it goes awry, contributes to the evolution of metastatic cancer.
 
Description RS Working group's document on Animate matter published
Geographic Reach National 
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 CRUK multidisciplinary award
Amount £500,000 (GBP)
Organisation University College London 
Department MRC Laboratory for Molecular Cell Biology
Sector Academic/University
Country United Kingdom
Start 01/2017 
End 12/2020
 
Description Keeping archaea young: elucidating the roles of proteostasis, secretion and division asymmetry in limiting replicative ageing in Sulfolobus.
Amount € 141,000 (EUR)
Funding ID ALTF_903-2021 
Organisation European Molecular Biology Organisation 
Sector Charity/Non Profit
Country Germany
Start 03/2022 
End 03/2024
 
Description Membrane remodelling during cell division in the thermoacidiophilic archaeaon Sulfolobus acidocaldarius
Amount € 141,000 (EUR)
Funding ID ALTF_1041-2021 
Organisation European Molecular Biology Organisation 
Sector Charity/Non Profit
Country Germany
Start 01/2022 
End 12/2023
 
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
 
Description evolution of vesicle trafficking
Amount £150,000 (GBP)
Funding ID LT001027/2019 
Organisation Human Frontier Science Program (HFSP) 
Sector Charity/Non Profit
Country France
Start 07/2019 
 
Title Archaeal genetics comes to the lab 
Description We are now one of the few labs in the world to do molecular genetics in Sulfolobus 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? No  
Impact In Saci we are now able to do i) tranformations ii) gene over-expression iii) dominant negative expression iv) mutagenesis v) CRISPRi 
 
Title Improved Sulfoscope by addition of SoRa and the development of new dyes for live imaging 
Description We improved the Sulfoscope for archaeal live cell imaging 
Type Of Material Technology assay or reagent 
Year Produced 2021 
Provided To Others? Yes  
Impact We have shared the method extensively with the community 
 
Title Sulfoscope 
Description We have developed the first microscope for imaging extremophiles. We can image 1 micron cells at 75°C 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? No  
Impact This promises to open up archaeal and extremophile cell biology. 
 
Title first live imaging of archaea 
Description We developed the first live imaging platform for extremophiles 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? Yes  
Impact We posted it on biorxiv 
URL https://www.biorxiv.org/content/10.1101/2020.02.18.953042v1
 
Description Archaeal cell-cell interactions and their role in the emergence of eukaryotes 
Organisation Brandeis University
Country United States 
Sector Academic/University 
PI Contribution We have come together to use archaea as a model of eukaryogenesis
Collaborator Contribution We co-wrote a grant that I lead
Impact none as yet
Start Year 2019
 
Description Archaeal cell-cell interactions and their role in the emergence of eukaryotes 
Organisation Dutch Research Council
Department Royal Netherlands Institute for Sea Research
Country Netherlands 
Sector Academic/University 
PI Contribution We have come together to use archaea as a model of eukaryogenesis
Collaborator Contribution We co-wrote a grant that I lead
Impact none as yet
Start Year 2019
 
Description Archaeal origins of eukaryotic cell organisation 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Academic/University 
PI Contribution Am leading a Wellcome collaboration
Collaborator Contribution Am leading a collaboration for Wellcome funding
Impact none yet
Start Year 2015
 
Description Archaeal origins of eukaryotic cell organisation 
Organisation University of Warwick
Country United Kingdom 
Sector Academic/University 
PI Contribution Am leading a Wellcome collaboration
Collaborator Contribution Am leading a collaboration for Wellcome funding
Impact none yet
Start Year 2015
 
Description Arnaud Echard at the Pasteur 
Organisation Pasteur Institute, Paris
Country France 
Sector Charity/Non Profit 
PI Contribution Working together on ESCRTIII-dependent abscission in human cells.
Collaborator Contribution Ongoing work to test ideas from studying division in TACK archaea in eukaryotes
Impact We are woring together on a paper
Start Year 2020
 
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 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 Gordon and Betty Moore Foundation grant to study symbiosis 
Organisation Dutch Research Council
Department Royal Netherlands Institute for Sea Research
Country Netherlands 
Sector Academic/University 
PI Contribution We were awarded a grant as part of the Symbiosis in Aquatic Systems Initiative.
Collaborator Contribution the collaboration is led by Anja Spang, it includes Dina Grohmann, Harald Huber and Laura Villanueva
Impact We are starting to share ideas and resources
Start Year 2020
 
Description Guillaume Charras's lab - studying mitotic cortex 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution We have 2 joint students on the CoMPLEX PhD programme working on monolayers
Collaborator Contribution They have developed the technology
Impact ideas, technology, training
Start Year 2011
 
Description Jeremy Carlton 
Organisation King's College London
Department Division of Imaging Sciences and Biomedical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution We are discussing the role of ESCRTIII in abscission with Jeremy. We also have a joint PhD student who is working on a related project.
Collaborator Contribution So far its just discussion
Impact The collaboration is interdisciplinary. They are focusing on the biochemistry and we are focusing on the mechanics.
Start Year 2016
 
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 Simon Walker-Samuel 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution We are working together to study cancer cell divisions in a tissue context.
Collaborator Contribution We will be co-supervising a CRUK studentship towards this end.
Impact Will be co-submitting a Wellcome consortium grant on this topic
Start Year 2019
 
Description Sonja Albers lab 
Organisation Albert Ludwig University of Freiburg
Country Germany 
Sector Academic/University 
PI Contribution We have had people exchange
Collaborator Contribution We have had people exchange and are drafting a joint project
Impact none yet
Start Year 2017
 
Description Sulfolobus - AC Lindas 
Organisation Stockholm University
Country Sweden 
Sector Academic/University 
PI Contribution Dr AC Lindas has been helping us to use Sulfolobus as a model system at the MRC LMCB.
Collaborator Contribution They have provided us with advice and reagents.
Impact This has helped us to win two grant awards: The Wellcome collaborative award and a BBSRC grant.
Start Year 2015
 
Description Sulfolobus - UCL 
Organisation University College London
Department MRC Laboratory for Molecular Cell Biology
Country United Kingdom 
Sector Academic/University 
PI Contribution Finn Werner and Rob de Bruin have been working together with us in establishing Sulfolobus as a model system at the LMCB.
Collaborator Contribution They have helped us with protocols and reagents.
Impact We now have Sulfolobus growing!
Start Year 2015
 
Description Tim Meyer - mitotic rounding in cancer 
Organisation University College London
Department UCL Cancer Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Working together to develop ways to study division in primary human tissue. We generated preliminary data showing that Ras affects mitotic cell rounding, mitotic cortical compliance and the sensitivity of cancer cell division to confinement.
Collaborator Contribution Primary patient data, the use of novel technology. Recruitment of an oncologist Masters student.
Impact Methodology development. Tim Meyer and I have been awarded a CRUK Clinical PhD Fellowship to work on "The role of oncogenic transformation on the environmental independence of cancer cell divisions" For this we will be recruiting a PhD student to begin later this year or early next year. The idea will be to determine how EGF-Ras signalling affects mitotic rounding and mitotic cell mechanics.
Start Year 2013
 
Description Tissue stretching 
Organisation University College London
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 VW Life? 
Organisation Albert Ludwig University of Freiburg
Department Centre for Biological Signalling Studies (BIOSS)
Country Germany 
Sector Academic/University 
PI Contribution We were recently awarded a VW Life? award. Towards this we contributed to writing of the grant and preliminary data.
Collaborator Contribution the grant is led by Sonja-Verena Albers, and the team includes Jan Löwe, Lars-Oliver Essen and Andela Saric
Impact Thus far we have only started with the award of this grant. We have also had one group meeting.
Start Year 2019
 
Description VW Life? 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Academic/University 
PI Contribution We were recently awarded a VW Life? award. Towards this we contributed to writing of the grant and preliminary data.
Collaborator Contribution the grant is led by Sonja-Verena Albers, and the team includes Jan Löwe, Lars-Oliver Essen and Andela Saric
Impact Thus far we have only started with the award of this grant. We have also had one group meeting.
Start Year 2019
 
Description VW Life? 
Organisation Philipp University of Marburg
Country Germany 
Sector Academic/University 
PI Contribution We were recently awarded a VW Life? award. Towards this we contributed to writing of the grant and preliminary data.
Collaborator Contribution the grant is led by Sonja-Verena Albers, and the team includes Jan Löwe, Lars-Oliver Essen and Andela Saric
Impact Thus far we have only started with the award of this grant. We have also had one group meeting.
Start Year 2019
 
Description Wellcome consortium to study achaeal origins of eukaryotic cell organisations 
Organisation Harvard University
Country United States 
Sector Academic/University 
PI Contribution I lead this Wellcome funded consortium that includes: Jan Lowe, Ricardo Henriques, Ann Christin Lindas, Thijs Ettema, Ethan Garner, Mohan Balasubramanian
Collaborator Contribution We are working together
Impact We have published a review, have held meetings, and are developing ideas and projects.
Start Year 2016
 
Description Wellcome consortium to study achaeal origins of eukaryotic cell organisations 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Academic/University 
PI Contribution I lead this Wellcome funded consortium that includes: Jan Lowe, Ricardo Henriques, Ann Christin Lindas, Thijs Ettema, Ethan Garner, Mohan Balasubramanian
Collaborator Contribution We are working together
Impact We have published a review, have held meetings, and are developing ideas and projects.
Start Year 2016
 
Description Wellcome consortium to study achaeal origins of eukaryotic cell organisations 
Organisation Stockholm University
Country Sweden 
Sector Academic/University 
PI Contribution I lead this Wellcome funded consortium that includes: Jan Lowe, Ricardo Henriques, Ann Christin Lindas, Thijs Ettema, Ethan Garner, Mohan Balasubramanian
Collaborator Contribution We are working together
Impact We have published a review, have held meetings, and are developing ideas and projects.
Start Year 2016
 
Description Wellcome consortium to study achaeal origins of eukaryotic cell organisations 
Organisation University of Warwick
Country United Kingdom 
Sector Academic/University 
PI Contribution I lead this Wellcome funded consortium that includes: Jan Lowe, Ricardo Henriques, Ann Christin Lindas, Thijs Ettema, Ethan Garner, Mohan Balasubramanian
Collaborator Contribution We are working together
Impact We have published a review, have held meetings, and are developing ideas and projects.
Start Year 2016
 
Description Wellcome consortium to study achaeal origins of eukaryotic cell organisations 
Organisation Uppsala University
Country Sweden 
Sector Academic/University 
PI Contribution I lead this Wellcome funded consortium that includes: Jan Lowe, Ricardo Henriques, Ann Christin Lindas, Thijs Ettema, Ethan Garner, Mohan Balasubramanian
Collaborator Contribution We are working together
Impact We have published a review, have held meetings, and are developing ideas and projects.
Start Year 2016
 
Description ASCB / EMBO 2021 
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 I co-organised ASCB/EMBO 2021.
It was the first online meeting of its kind and was a great success.
Year(s) Of Engagement Activity 2020
 
Description BBC: the language exchange 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Was one of the two participants in a new programme: the language exchange, where scientists interact with poets,
Year(s) Of Engagement Activity 2021
URL https://www.bbc.co.uk/programmes/m0011rn9
 
Description BPPB biophysics seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented to international biophysics community
Year(s) Of Engagement Activity 2020
 
Description Lecture to Phd students at Pasteur as part of international phd programme 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Gave seminar on evolution
Year(s) Of Engagement Activity 2020
 
Description PhD student seminar at IGC portugal on morphogenesis 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact taught students
Year(s) Of Engagement Activity 2020
 
Description Plenary Talk at ls2 zurich 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary talk at annual swiss/austrian cell biology meeting
Year(s) Of Engagement Activity 2020
 
Description Talk : Cambridge morphogenesis club 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact I presented our recent work
Year(s) Of Engagement Activity 2021
 
Description Talk at ASCB 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave a talk at ASCB, the world's largest and most important cell biology meeting
Year(s) Of Engagement Activity 2021
 
Description Talk on evolution IGC portugal 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk about evolution of cell division
Year(s) Of Engagement Activity 2020
 
Description University of Penn talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk about recent work
Year(s) Of Engagement Activity 2021
 
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 APS 
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 the annual APS conference
Year(s) Of Engagement Activity 2021