AUTOMATIC CONTROL OF MAMMALIAN GENE EXPRESSION USING A MICROFLUIDIC PLATFORM
Lead Research Organisation:
University of Bristol
Department Name: Engineering Mathematics and Technology
Abstract
ITALY
ITALY
ITALY
People |
ORCID iD |
| Lucia Marucci (Principal Investigator) |
Publications
Khazim M
(2021)
A Microfluidic/Microscopy-Based Platform for on-Chip Controlled Gene Expression in Mammalian Cells.
in Methods in molecular biology (Clifton, N.J.)
Postiglione L
(2018)
Regulation of Gene Expression and Signaling Pathway Activity in Mammalian Cells by Automated Microfluidics Feedback Control.
in ACS synthetic biology
| Description | This funding allowed getting relevant training in mammalian cell external control, which resulted in the generation of data about the control of stem cells using microfluidics devices. The objectives of the grant were met; this award facilitated preparation of further grant proposals, and results obtained with the platform we set-up have been recently published. |
| Exploitation Route | The RAs in my group, thanks to the training received, have set-up a microfluidics/microscopy platform in Bristol. My group is currently performing experiments using the platform, and other researchers at Bristol University have been also trained to use it. |
| Sectors | Education,Pharmaceuticals and Medical Biotechnology |
| Description | The platform we set-up, thanks to training received through this award, was used in public engagement activities facilitated by Bristol University. |
| First Year Of Impact | 2018 |
| Sector | Education |
| Impact Types | Cultural |
| Description | Engineering for a prosperous nation |
| Amount | £250,704 (GBP) |
| Funding ID | EP/R041695/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2018 |
| End | 05/2019 |
| Description | Horizon 2020 FET-Open action "Control Engineering of Biological Systems for Reliable Synthetic Biology Applications" |
| Amount | € 3,000,000 (EUR) |
| Funding ID | Grant agreement ID: 766840 |
| Organisation | European Commission |
| Department | Horizon 2020 |
| Sector | Public |
| Country | European Union (EU) |
| Start | 10/2017 |
| End | 09/2020 |
| Title | Algorithms for cell segmentation |
| Description | We developed multiple algorithms for microscopy image segmentation (De Cesare et al, ACS Omega 2021; Pedone et al. ACS Synthetic Biology 2021). All code is open source |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | Automatic control of gene expression in mammalian cells, using online segmentation algorithms. |
| URL | https://github.com/BiocomputeLab/cheetah |
| Title | Automatic feedback control of gene expression in mammalian cells |
| Description | We developed a microfluidics/microscopy platform to measure and control gene expression in mammalian cells. This, in turns, required specialised software for online cell segmentation, control and actuation. |
| Type Of Material | Model of mechanisms or symptoms - in vitro |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | The methodology can be used to track dynamics in living mammalian cells, and to automatically infer improved protocols. Results published in Postiglione et al, ACS Synth. Biol. 2018, 7, 11, 2558-2565. |
| URL | https://pubs.acs.org/doi/abs/10.1021/acssynbio.8b00235 |
| Title | Inducible system to perturb gene expression |
| Description | The proposed inducible system allows modulating independently gene expression and protein stability by the addition of two orthogonal drugs. |
| Type Of Material | Model of mechanisms or symptoms - in vitro |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | We used the tool to demonstrate the role of signalling pathway does in embryonic stem cell fate (DOI 10.1016/j.isci.2022.103756) |
| Title | Algorithms for cell segmentation |
| Description | We developed new algorithms for cell segmentation, based on the Otsu methods (De Cesare et al. ACS Omega 2021) and deep-learning (Pedone et al. ACS Synthetic Biology 2021). |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | These algorithms enabled robust automatic feedback control of living cells. |
| URL | https://www.github.com/BiocomputeLab/cheetah |
| Description | Collaboration on mammalian cell control |
| Organisation | Telethon Foundation |
| Department | Telethon Institute of Genetics and Medicine (TIGEM) |
| Country | Italy |
| Sector | Charity/Non Profit |
| PI Contribution | My team has contributed to this collaboration by generating preliminary feedback control experiments in mouse embryonic stem cells, using a microfluidics device, an actuation platform and control algorithms. |
| Collaborator Contribution | The partner has provided segmentation/control algorithm code, and hosted 2 RAs in my group in his lab for 10 days. |
| Impact | The collaboration is multidisciplinary (e.g. involves combination of experimental work, and modelling/programming work). Results from this collaboration have been included in 3 publications (De Cesare et al, ACS Omega 2021; Postiglione et al. ACS Synthetic Biology 2018; Pedone et al. Nature Communications 2019). |
| Start Year | 2017 |
| Title | Computational toolkit for cybergenetic control |
| Description | The computational platform allows integrated online cell segmentation and control. |
| Type Of Technology | Software |
| Year Produced | 2021 |
| Open Source License? | Yes |
| Impact | The code is open-source and easy to modify/adapt for other cell lines and microscopy settings. |
| URL | https://pubs.acs.org/doi/abs/10.1021/acssynbio.0c00463 |
| Description | Invited Seminar, Sheffield University, January 2023 (in person) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited talk to the Department of Chemical and Biological Engineering; attended by PhD students, postdocs and academics. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Invited talk, EMBO workshop "Network inference in biology and disease" |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Workshop bringing together interdisciplinary researchers in biotechnology, bioinformatics, systems biology and synthetic biology. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://meetings.embo.org/event/19-network-inference |
| Description | Open Days Engineering, Bristol University (UK) |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | Open Days for A level students, which involved presentations by PhD students and PDRAs, and demos. |
| Year(s) Of Engagement Activity | 2017,2018,2019,2020 |
| Description | Oral Presentation, 2021 Virtual International Mammalian Synthetic Biology Workshop |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Research conference |
| Year(s) Of Engagement Activity | 2021 |
| URL | http://mammalian-synbio.org/2021 |
| Description | Oral Presentation, Dynamics Days Digital 2020 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Conference attended mainly by academics |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.danieleavitabile.com/ddd2020/ |
| Description | Oral Presentation, Research Conference, 18th European Control Conference (ECC) 2019, Naples (Italy). |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Interdisciplinary conference about principles and applications of control engineering. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://ecc19.eu/ |
| Description | Oral Presentation, Research Conference, Foundations of Systems Biology in Engineering (FOSBE) 2019 |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Research conference on applications of control engineering in Systems and Synthetic Biology; interdisciplinary audience. |
| Year(s) Of Engagement Activity | 2019 |
| URL | http://fosbe2019.ai2.upv.es/ |
| Description | Oral Presentation, Synthetic Biology UK (SBUK), Bristol 2018 |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Most relevant Synthetic Biology conference in UK; interdisciplinary audience. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.eventsforce.net/biochemsoc/frontend/reg/thome.csp?pageID=18045&eventID=43&traceRedir=2 |
| Description | Oral Presentation, Synthetic Biology: Engineering, Evolution & Design (SEED), 2019, New York (US) |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Interdisciplinary conference on Synthetic Biology. |
| Year(s) Of Engagement Activity | 2019 |
| URL | http://synbioconference.org/2019 |
| Description | Talk at "Multi-agent modeling meets synthetic biology" workshop |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Workshop held at the University of Bristol, UK and funded by BrisSynBio, a BBSRC/EPSRC Synthetic Biology Research Centre (Grant No. BB/L01386X/1). It was attended by key UK experts in agent-based modelling of biological systems; it sparked discussions about the use of multiscale frameworks in synthetic biology. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://doi.org/10.3389/fbioe.2020.00705 |