AUTOMATIC CONTROL OF MAMMALIAN GENE EXPRESSION USING A MICROFLUIDIC PLATFORM

Lead Research Organisation: University of Bristol
Department Name: Engineering Mathematics

Abstract

ITALY
ITALY

Publications

10 25 50
 
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 09/2017 
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 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