Harnessing Nature's ability to create membrane compartmentalisation through redesign of a protein machinery.
Lead Research Organisation:
University of Leeds
Department Name: Sch of Chemistry
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
People |
ORCID iD |
| Paul Beales (Principal Investigator) |
Publications
Aguilar M
(2021)
Behaviour and interactions of proteins and peptides with and within membranes; from simple models to cellular membranes: general discussion.
in Faraday discussions
Aguilar M
(2021)
Peptide-membrane interactions and biotechnology; enabling next-generation synthetic biology: general discussion.
in Faraday discussions
Aguilar M
(2021)
Theoretical and experimental studies of complex peptide-membrane systems: general discussion.
in Faraday discussions
Arribas Perez M
(2021)
Biomimetic Curvature and Tension-Driven Membrane Fusion Induced by Silica Nanoparticles
Arribas Perez M
(2021)
Biomimetic Curvature and Tension-Driven Membrane Fusion Induced by Silica Nanoparticles.
in Langmuir : the ACS journal of surfaces and colloids
Beales P
(2017)
Durable vesicles for reconstitution of membrane proteins in biotechnology
in Biochemical Society Transactions
Beales P
(2018)
The artificial cell: biology-inspired compartmentalization of chemical function
in Interface Focus
Beales PA
(2017)
Biophysics: A toehold in cell surface dynamics.
in Nature nanotechnology
Beales PA
(2018)
The artificial cell: biology-inspired compartmentalization of chemical function
in Interface Focus
| Title | Archibio Blueprints |
| Description | A collaboration between artists, scientists and an architect. This artwork compares structure and function between architecture and biology. The output are architectural plans of a bacterium made using traditional blueprinting methods. |
| Type Of Art | Artwork |
| Year Produced | 2017 |
| Impact | This has been displayed at multiple art and science festivals, including ASMbly 2017 (Leeds), Otley Science Festival (2017) and the Astbury Conversation public engagement event (2018). As well, it has been advertised through social media (Twitter) and will feature in an upcoming book on the Superposition. |
| Title | Kinetic sculture (Jim Bond) |
| Description | We have engaged with a local artist to create a piece that would help us to engage the public on the research topic of the grant. The piece has been commissioned and the artist has met with both teams (Leeds and Sheffield) to gauge the essence of our work. The artwork has not been completed yet but when it will be finished, we plan to show it at science festivals. |
| Type Of Art | Artefact (including digital) |
| Year Produced | 2017 |
| Impact | The interaction with the artist has forced us to open new perspectives on our science. |
| URL | http://www.jimbond.co.uk/ |
| Description | We aimed to develop a system for compartmentalization of cargo within complex membrane architectures, such a vesicle within a vesicle. These architectures are useful for multiple purposes, in particular for the advancement of artificial cell technologies where biomimetic functions can be built into cell-like architectures from the bottom-up. The multicompartment nature of these architectures is reminiscent of the eukaryotic cell, which supports the simultaneous function of multiple incompatible chemistries in isolation yet in close communication. Our vision is that these architectures and their highly addressable assembly strategies will form an essential platform technology for advanced functional materials applied to wide-ranging (bio)chemical industries, including medical technologies, environmental remediation, diagnostic biosensors and manufacture of fine chemicals. We set about repurposing a biological machinery (the ESCRT complex) to demonstrate that it is possible to dynamically control the formation of a vessel containing internal compartments encapsulating different chemistry. (1) We aimed to generate a proof of concept system can create multicompartment structures containing different chemical environment. This was achieved by repurposing ESCRT proteins in a minimal vesicle system, utilising an energy-dependent ATP-ase (Vps4) to recycle the complex for subsequent rounds of encapsulation of different chemical cargoes. (2) We aimed to minimize the number of components necessary for creating these membrane architectures on-demand. We have achieved this by designing one molecule incorporating the key features provided normally by multiple different molecular components of the ESCRT complex. This all-in-one ESCRT protein has much greater membrane remodelling activity than the core ESCRT component, Snf7. (3) A major goal of our work was to gain some predictive control of the activity of these membrane remodelling complexes to optimise our ability to regulate the formation and architectures of multicompartment vesicles. We anticipated this would be achieved through varying the relative stoichiometry of different molecular components of the complex. Our major new finding was that the membrane is an active player in this process such that it mechanically regulates the assembly and function of ESCRT proteins, yielding far greater control than stoichiometric variation. Optimisation required an in-depth understanding of how physical parameters (membrane mechanics) impact the biological activity (protein assembly). Our discovery of a mechanical modulatory mechanism beyond the stoichiometric control has key implications for both the controlled construction of artificial cells and provides insights that generate new hypotheses in how we interpret the fundamental molecular cell biology of membrane trafficking and homeostasis. |
| Exploitation Route | Researchers in the bioengineering community that aim to construct an artificial cell will be spurred to develop synthetic systems which repurpose this and other native membrane remodelling machineries to construct complex cell-like architectures, where uptake and release of molecules is regulated by membrane tension. In turn, these systems could be developed for a variety of industry applications, including drug delivery, environmental remediation, chemical sensing. The physical sciences community will be inspired to investigate the physics behind the relationship between membrane mechanics and molecular assembly. Deeper insights into the interplay between physical forces and biochemical function is essential to understanding the physics of life in molecular detail. The biology community considers membrane tension as a key regulator in uptake and release of molecules by cells. We have now provided a molecular rationale for this and we anticipate the rules we have provided for ESCRT activity can be applied to interpret how diverse biological complexes function (or malfunction). |
| Sectors | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology,Other |
| Description | There is now a growing drive in the artificial cell / bottom-up synthetic biology community to develop highly compartmentalised synthetic cell-like materials, where we have driven early work in this area through our demonstration of the repurposing of ESCRT protein machinery to remodel the membranes of synthetic vesicles into multicompartment structures. The insight we have provided on the membrane-controlled mechanisms of ESCRT function (e.g. membrane tension as a negative feedback regulation mechanism; remodelling of phase separated vesicles preferentially creating internal compartments with liquid ordered membranes) have inspired further research on the biophysical mechanisms of action of ESCRT proteins. For example, cell biologists have since shown that the tension-regulated feedback mechanism we report in model membranes is relevant to analogous mechanisms active in living cells: "Endosomal membrane tension regulates ESCRT-III-dependent intra-lumenal vesicle formation" published in Nature Cell Biology (https://doi.org/10.1038/s41556-020-0546-4). Furthermore, our findings on the invagination of liquid ordered membranes by ESCRTs have been deemed surprising and interesting enough for other groups to reproduce this work (https://doi.org/10.1016/j.bbamem.2021.183689). The tools we have established for the engineering biology approaches to artificial cells can now be practically implemented by the wider field and will be the subject of further development and enhancement research in the future. Our innovative art-science outreach commission, Vessel, has inspired further similar outreach activities. This commission featured in a book about the pioneering collaborations of artists, scientists and makers in Leeds in a collaborative network called The Superposition (ISBN: 978-1-910846-05-6). Since then, art-science collaborations have been on the increase with the University of Leeds and nationally as an innovative approach to engage the public with science through art and has led to several further collaborations for Dr Beales, including a glass sculptor and a creative writer/poet. |
| First Year Of Impact | 2020 |
| Sector | Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Cultural |
| Description | BBSRC CBMNet travel bursary |
| Amount | £200 (GBP) |
| Organisation | CBMNet |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 02/2018 |
| End | 02/2018 |
| Description | EPSRC Impact Acceleration Account - (Insplorion) |
| Amount | £24,248 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2019 |
| End | 03/2020 |
| Title | Dataset associated with 'Biomimetic curvature and tension-driven membrane fusion by silica nanoparticles' |
| Description | Experimental data obtained from FRET spectroscopy and confocal microscopy imaging of lipid vesicles interacting with silica nanoparticles. Experimental set up and data processing and analysis described in the publication in Langmuir. Confocal microscopy movies of giant unilamellar vesicles undergoing fusion upon interaction with silica nanoparticles. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://archive.researchdata.leeds.ac.uk/905/ |
| Description | Creative Labs collaboration with Dr Caitlin Stobie |
| Organisation | University of Leeds |
| Department | School of English |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Research discussions and data sharing for the purposes of inspiring creative outputs for use in public dissemination. We have also been discussing concepts in new materialism and how ideas of agency of non-living matter and the blurring of lines between living and non-living matter in bottom-up synthetic biology may relate to the ethics of research into making an artificial cell. We have also been using this philosophical framework to discuss implications for developing materials (e.g. synthetic peptides or nanovesicles) that interact with living organisms in biomedical applications. |
| Collaborator Contribution | Philosophical discussions related to new materialism and research ethics in research into making an artificial cell and materials for use in biomedical applications as well as producing creative outputs (poems and short stories) related to ongoing research projects in the Beales group. |
| Impact | Visual poem: grimace scale (three-in-one poem written on three colour confocal microscopy image) - subdivides into three colour poems Grim, Ace and Scale. Visual poem: frozen in time and space (poem written on an electron micrograph of a vesicle) |
| Start Year | 2019 |
| Description | Hojo/Tamagaki (Osaka) - pH-switchable transmembrane peptides |
| Organisation | Osaka University |
| Department | Institute of Protein Research |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | This collaboration was agreed during the Astbury-IPR visit to Osaka in May 2018 where we presented our work on ESCRT-mediated membrane remodelling to create compartmentalised artificial cells. The collaboration is currently funded by an Astbury-IPR pump-priming fund (£6k for consumables and travel). My group are looking at pH-switchable transmembrane peptides (provided by IPR) to study their switchable domain partitioning in phase separated giant vesicle membranes. These peptides have the potential to be developed into novel synthetic biology tools for functional artificial cells. |
| Collaborator Contribution | The Osaka team of Hironobu Hojo and Hiroko Tamagaki at IPR are synthesising their peptides and performing initial characterisation by fluorescence/IR/NMR spectroscopies. |
| Impact | The pump-priming project is ongoing. This is an interdisciplinary biochemistry/biophysics collaboaration. |
| Start Year | 2018 |
| Description | Microfluidics collaboration - Prof Stephen Evans |
| Organisation | University of Leeds |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | The aim is to develop a microfluidic vesicle trapping device that will maintain low membrane tension when vesicles are trapped and allow exchange of external media for generation of artificial cell models. Contribution from our labs is the time of a PDRA for experiments and analysis, GUVs and ESCRT protein samples. |
| Collaborator Contribution | Contributions from Steve Evans' group are the time of a PDRA for making microfluidic chips, doing experiments and access to necessary flow pumps. |
| Impact | Ongoing work. This is multidisciplinary (physics/chemistry/biochemistry) |
| Start Year | 2018 |
| Description | Prof P Lusk (Yale) |
| Organisation | Yale University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We have provided preliminary data supporting the hypothesis that specific lipids are involved in the recruitment of ESCRT-III proteins to membranes |
| Collaborator Contribution | The Lusk group has world-class expertise in the mechanisms of nuclear envelope membrane repair in yeast. They validated our preliminary data in the yeast model. |
| Impact | These data have been used for a grant application to BBSRC in collaboration with the Yale group. |
| Start Year | 2018 |
| Description | Shinohara (Osaka) - phosphorylation induced membrane binding of SUN domain peptides |
| Organisation | Osaka University |
| Department | Institute of Protein Research |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | This collaboration was agreed during the Astbury-IPR meeting in Osaka in May 2018. We presented the ESCRT-mediated compartmentalisation of GUV artificial cells at this meeting. This collaboration with the group of Akira Shinohara is to understand the phosphorylation-induced changes in membrane-binding of SUN domain peptides. We envisage that these peptides can be developed into a synthetic biology toolkit for switchable membrane association of peptide-associated cargo that could be adapted with the ESCRT cargo encapsulation method. We are developing FRET-based membrane binding assays for these peptides and investigating their interaction with GUV membranes, including domain partitioning studies in phase separated vesicles. |
| Collaborator Contribution | The Osaka team of Akira Shinohara are synthesising the peptides and performing initial biochemical characterisation before sending them to Leeds for biophysical membrane assays. |
| Impact | Collaboration ongoing. Interdisciplinary biochemistry/biophysics collaboration. |
| Start Year | 2018 |
| Description | Advertising the art commission through Facebook |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | The art commission was advertised on Facebook through the local art-science collaborative network, the Superposition.This was viewed 3314 times, with 31 shares including by Monica Bello who is head of arts at CERN. This led to national and international enquiries about the commission and 60 complete applications from local, national and international artists. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Archibio Blueprints at Otley Courthouse |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | As part of the Otley Science Festival 2017, our collaborative science-inspired artwork "Archibio Blueprints", inspired by building biology through bottom-up approaches, was displayed at the Otley Courthouse theatre and events venue for the months of November as part of a larger science-inspired art exhibition. We estimate that well in excess of 1000 visitors will have seen the exhibition over the month it was displayed for. The curator at the Otley Courthouse was keen to discuss future exhibitions and art-science collaborative workshop events at the venue, so this may become a more regular event. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Art installation (Light Night - Leeds) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Presentation at 'Light Night' in Leeds of the artwork 'vessel' inspired from the funded EPSRC project. Light Night Leeds is an annual free multi-arts festival. Postdoc Andrew Booth, PI Dr B Ciani, artist Jim Bond and PI Dr P Beales engaged with the public explaining the project behind the inspiration for 'Vessel'. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.leeds.ac.uk/info/4000/around_campus/453/light_night |
| Description | Art-science commissioning process |
| 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 | Applications for the art-science commission were submitted through the Curator Space website. 60 artists applied, mainly from the UK but a small number were international submissions. A commissioning panel consisting of the two scientific lead investigators on the project and three local artists from the Leeds greater region met in Leeds to decide who would be awarded the commission. This led to an interesting two way dialogue as to what would make a good piece of artwork to present at festivals for public engagement with the science. Both scientists and artists learnt a lot from the process and as we understood each other's perspectives we quickly narrowed down a field of very high quality submissions. Interestingly very few splits in opinion were along the artist/scientist divide of the panel and the outcome was a final decision that all on the panel were very happy with. The kinetic sculpture that has now been commissioned is a work in progress to be finished and presented later in 2017. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Blog on art-science collaboration |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Blog post of personal reflections on the challenges and benefits of art-science collaboration, featuring discussion of Vessel, a funded commission on this EPSRC grant. Several colleagues have discussed this with me since in my own institution and at conferences with interest in using art as a mechanism for engaging the wider public. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://academicdadblog.wordpress.com/2017/11/12/the-art-of-science-engagement/ |
| Description | Display at Vessel at Royal Society's Chicheley Hall (Feb 2018) |
| 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 | Vessel was displayed at Royal Society's Chicheley Hall during the focussed workshop "the Artificial Cell". It raised further attention to our work while also introducing the concept of art as a medium for science engagement to many academics, postdocs and pdras at the meeting. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Display of Vessel (art-science collaboration) in School of Chemistry, University of Leeds |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Undergraduate students |
| Results and Impact | Vessel spent two weeks installed in the School of Chemistry opposite the central social area and in a main thoroughfare to the large lecture theatres. It was viewed by staff, students, visitors (including UCAS applicants). Staff members showed interest in using art as a medium for engagement and students showed interest in the science. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Display of Vessel and Archibio blueprints at Astbury Conversation public engagement event |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | We displayed a collection of science-inspired collaborative art projects, mostly conducted through the Superposition network, at the public engagement event of The Astbury Conversation at the University of Leeds. This event is aligned with a Nobel Laureate public lecture and draws in public, schools and academics as major audiences. The art on display included Vessel, a directly funded commission from this grant, and Archibio Blueprints, a further collaborative art project that we have been involved in that relates to synthetic biology with the idea of building biology - also directly relevant to the research on this grant. There were in excess of 200 attendees at the event. The exhibition allowed members of the public to engage with science in new ways, through engaging with art work, and led to many questions and ideas from the public about both the science and the art. It also demonstrated to academic colleagues the benefits of public engagement with science through art. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Display of Vessel at ASMbly 2017 (art-science public dissemination) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Art-science commission "Vessel" debuted at ASMbly lab 2017 in an empty shop in St Johns Centre in Leeds. This 2 week art-science-maker festival (26th July - 7th August) consisted of project workspace, an exhibition, workshops and special events. Interesting discussions about the science and the art-science collaborative process took place with artists, other scientists and the general public. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.thesuperposition.org/asmblylab2017/ |
| Description | Interview for social media |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Postdoc Andrew Booth, PI Dr B Ciani, artist Jim Bond were interviewed on Instagram Live by the Light Night crew to explain the project behind the inspiration for 'Vessel'. Audience engaged in a live Q&A session |
| Year(s) Of Engagement Activity | 2017 |
| Description | Light Night Leeds 2021 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Light Night Leeds is the UK's largest annual arts and light festival. It takes place over two nights in October. Our collaborative creative outputs with poet and short-story writer Dr Caitlin Stobie, where poems inspired by the research are written onto research images from the project were edited into a 5 minute video by Stephen Manthorp from the University of Leeds' Cultural Institute. This video was projected onto the facade of the Leeds Library in the centre of Leeds as one of the exhibitions for Light Night 2021. The event attracts a large audience from across the region to see the art and light installations positioned across the city. The video for our Blurred Lines collaboration featured research outputs from several UKRI funded projects in my group on developing artificial cells for engineering biology and medical applications of soft matter. The installation was also featured within wider Light Night media, including local TV, newspaper and online social media publicity. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Organised "The Artificial Cell" topical session at the 2021 SoftComp annual meeting (online) |
| 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 | Dr Beales organised and chaired a topical session on "The Artificial Cell", inviting leading academics across Europe and also featuring research on membrane remodelling from Dr Beales' group, presented by a PhD student. The conference was the annual meeting of the SoftComp network, which is a European network interested in soft matter composites. The conference took place online due to COVID restrictions. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Presenting art-science commission (Leeds) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Postdocs Andrew and Chris presented the project and the art commission competitiom to an artist network in Leeds (~30 people). We had a large number of applications from artists for the commission (~60 national and international applications). |
| Year(s) Of Engagement Activity | 2016 |
| Description | Presenting art-science commission (Lowry, Manchester) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | A 10 minute talk was given at an art-science event at the Lowry in Manchester to an audience of ~40 people detailing the science of the project and the art-science commission competition for £2000 to produce a piece of artwork inspired by the project that could be displayed at both science and art festivals to engage a wide audience. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.thesuperposition.org/portfolio-item/superposition-the-lowry/ |
| Description | Short story published by Dr Caitlin Stobie that features our research on artificial cell compartmentalisation |
| 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 | As part of our "Blurred Lines" creative labs collaboration exploring concepts related to the artificial cell and the blurred lines between non-living and living matter, Dr Caitlin Stobie wrote a story of a scientist and her partner during lockdown where the scientist is undertaking the research we recently published as part of the Faraday Discussions on peptide-membrane interactions (https://doi.org/10.1039/D0FD00042F). This is published online by ZenoPress and is freely available to the general public. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.zenopress.com/short-stories/h5qsrhkmjyhoo9vjp2hjzix2uhv2nf |
| Description | Website: Blurred Lines: Life, Matter, Poetry |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | As part of our collaboration with poet and short story writer, we have a public-facing website that details the poems and creative outputs of our collaboration. Blurred Lines: Life, Matter, Poetry is inspired by medical applications of soft matter, the science of artificial cells, and philosophical concepts from new materialism. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.blurredlinesleeds.co.uk/ |