Below is a list of the projects that we are currently recruiting for, to start in October 2021. More details on the application process can be found here.

Establishing a synthetic biology toolbox for biosensor development in important probiotic host organisms.

  • Lead supervisor: Prof. Geoff Baldwin (Imperial College London)
  • Co-supervisor: Dr Karen Polizzi (Imperial College London)

The fundamental impact of microbiome-based bacteria upon human health is increasingly understood. Dysbiosis is an imbalance of microbiome bacterial constituents that is strongly linked to the pathology of a wide range of conditions. This project will develop new approaches to rebalance the microbiome to treat and prevent such diseases. This project will engineer probiotic organisms to detect metabolic changes that are characteristic of pathologic states and trigger the deployment of appropriate treatments at the site of interest. This will require the development of engineering tools for probiotic lactic acid bacteria, as well as bioinformatics approaches to identify new sensing components required to create the required biosensors.

We currently lack the tools necessary to detect and selectively remove bacterial constituents of the microbiome that cause dysbiosis. This limits therapeutic intervention. Novel, next-generation therapeutic bacteria (NTB) capable of sensing and precisely resolving dysbiosis represent a new frontier in the treatment of microbiome related disorders. This project will develop key dysbiosis-sensing components to create new bacterial therapies, by creating a biosensing toolbox enabling genetic engineering of lactic acid bacteria that can sense and react to metabolic changes characteristic of microbiome dysbiosis. Ultimately, these bacterial biosensors will control the deployment of specific bactericidal payloads into the microbiome by NTB.

A bioinformatics approach will be taken to identify new sensing components that govern transcriptional regulation in response to external signals. These will then be repurposed as biosensors for the detection of the state of the microbiome. To better be able to engineer probiotic bacteria, a synthetic biology toolbox will be created for suitable hosts. For therapeutic use in the human microbiome, lactic acid bacteria such as Lactobacillus spp. are an ideal choice given their Generally Regarded As Safe (GRAS) status. However, few characterised promoters, ribosome binding sites, terminators and vectors are described for Lactobacillus spp., addressing this need will therefore transform our ability to reliably engineer these types of organism.

This project will be based at Imperial College London. It is also supported by CCBio, an innovative Synthetic Biology startup company, giving the student the opportunity to experience the industrial and commercial aspects of this project.

Engineering biological complexity in yeast: synthetic pattern formation and emergence 

  • Lead supervisor: Dr Naomi Nakayama (Imperial College London)
  • Co-supervisor: Prof. Tom Ellis (Imperial College London)

Engineering increased biological complexity is a key goal for biodesign engineering. Theoretical studies have uncovered simple mathematical rules that generate robust heterogeneity in spatial and temporal patterns within cell populations that can be considered as ‘engineering principles’. Division of labour and other forms of heterogeneity also underlie the emergent properties of a multicellular entity, often enabling higher efficiency as a whole in important functions like metabolism, transport, structural stability, and feedback control. An ambitious and timely challenge for synthetic biology is to understand how to reverse engineer and rationally design symmetry-breaking events and the emergent interactions that then follow in a community of cells.

This interdisciplinary project will develop synthetic biology tools to predictively design and instruct synthetic developmental decision-making in yeast. To control multicellular growth pattern and morphogenesis, we will use synthetic gene regulation to modulate the timing and frequency of cell division and growth, and to instruct orthogonal adhesion between sets of cells. Cells will be programmed to differentiate in response to cell-to-cell communication and to lateral activation/inhibition. In order to expand the modular DNA resources for engineering multicellular complexity, this project aims to create a novel molecular machine for a self-organising symmetry-breaking events.

To do this, we will transfer a well-characterised morphogen system from plants that provides a concentration-dependent molecular switch. In plants, accumulation of the hormone auxin coordinates differential cell fate and growth regulation. Auxin moves between cells with the aid of the efflux carrier PIN proteins, which show polar localisation within a cell. Auxin is already a well-established chemical inducer of synthetic gene regulation in the yeast. By introducing the PIN module into cells with auxin-regulated gene control, we will be able to program intercellular auxin flow and asymmetrical concentration gradient within a yeast colony. Data analysis of the images, videos, and flow cytometry data, along with Bayesian statistical methods will be used to generate parameters to populate mathematical models of the intracellular gene circuits and complementary agent-based models describing how the different cells interact, communicate and adhere.

This project will be based at Imperial College London.

icRNA: in vivo circular RNAs for efficient expression and control of genes and polyproteins

  • Lead supervisor: Prof. Guy-Bart Stan (Imperial College London)
  • Co-supervisor: Dr Tom Ouldridge (Imperial College London)
  • Co-supervisor: Dr Rodrigo Ledesma-Amaro (Imperial College London)

Potent, stable and controllable gene expression is a long-standing goal of synthetic biology. Thanks to Watson-Crick base pairing, RNA-based controllers have the potential to be more programmable and predictable, and to impose less metabolic burden to host cells compared to protein-based controllers. In microbes, however, RNA-based systems typically offer limited dynamic range and require high-levels of RNA expression due to the short half-lives of linear RNAs. This project aims to develop an RNA-based controller with a high dynamic range and low host burden by using in vivo circularisation and linearisation of mRNA. Circular RNAs (cRNAs) lack 5’ and 3’ ends, which eliminates end-dependent degradation by exoribonucleases and several endoribonucleases, causing cRNAs to exhibit far longer half-lives compared to linear mRNAs. However, due to a lack of efficient methods for in-vivo cRNA production, the use of cRNAs has been limited so far. 

This project will focus on the development of a novel in-vivo cRNA expression system in E. coli (and potentially in S. cerevisiae, too), adapting the Tornado RNA circularisation system to circularise long mRNAs. The main task of the project will be to rationally engineer the sequence of the ribozymes and transcripts to optimise cleavage and ligation. To further increase the dynamic range of the circuit, we will implement an RBS-repairing strategy where the RBS is initially split in two parts placed at the ends of the linear mRNA and gets repaired only when the RNA is circularised. In parallel with the experimental work, computational models accurately describing RNA circularisation and linearisation kinetics and circular mRNA translation dynamics will be built to understand and predict the dynamic behaviour of these RNA-circularisation systems. 

This cRNA control system will be used as a platform for controlling gene expression with applications in production of materials, therapeutics, and potentially vaccines. Additionally, by removing the stop codon from the coding sequence in a circular mRNA, rolling circle translation can be achieved, which can be used for the efficient production of valuable multi-unit repeat proteins with useful properties for the production of novel biomaterials.

This project will be based at Imperial College London.

Microfluidic platforms for the engineering of continuously-operating, synthetic nucleic acid-based systems

  • Lead supervisor: Dr Tom Ouldridge (Imperial College London)
  • Co-supervisor: Dr Claire Stanley (Imperial College London)
  • Co-supervisor: Prof. Guy-Bart Stan (Imperial College London)

Nucleic acid nanotechnology is a versatile platform for engineering molecular networks. By designing oligonucleotide molecules with specific sequences, one can build complex synthetic systems with predictable and programmable reactions. The most versatile networks are based on “strand displacement” reactions, in which base pairing is used to drive the replacement of one or more strands in a multi-stranded “gate complex”. The outputs of these displacement reactions can trigger subsequent reactions, allowing the construction of large networks.

Traditionally, the essential gate complexes are produced via a multi-step process that cannot be realised in situ. Individual strands are separately synthesized, annealed to form multi-stranded gates, and these gates are then mixed to create a network that produces a single fixed output. Traditional strand displacement-based networks cannot operate continuously without an external supply of gates produced in this way. This limitation prohibits their application in engineered or synthetic cells, where networks must continuously respond to their environment using components produced in situ and in real time.

We have recently demonstrated in situ production of multi-stranded RNA gate molecules directly from transcription, utilising self-cleaving RNA ribozyme motifs that convert a folded single-stranded RNA transcript into a multi-stranded complex [Bae et al., https://pubs.acs.org/doi/10.1021/acs.nanolett.0c03629]. These constructs have the potential to underlie continuously-operating strand displacement networks; this project aims to explore this potential using microfluidic “cells” that can sustain continuously-operating networks. The result will be a novel engineering platform for nucleic acid nanotechnologists, and also a vital step in the process of incorporating nucleic acid-based circuits into living cells.

The student will start by developing microfluidic platforms that are appropriate to hosting continuously active nucleic acid-based systems, identifying optimal geometries and materials for the challenge. Subsequently, the student will test nucleic acid-based circuits of increasing complexity in the microfluidic chips built. Both stages of the project will involve significant input from computational modelling; the project is therefore highly appropriate for students seeking an interdisciplinary challenge straddling engineering, nanotechnology and biology.

This project will be based at Imperial College London.

Engineering synthetic C1 utilisation in non-conventional organisms for sustainable bioproduction

  • Lead supervisor: Dr Rodrigo Ledesma-Amaro (Imperial College London)
  • Co-supervisor: Dr Patrik Jones (Imperial College London)

Climate change is likely the most serious threat thus far to the continued wellbeing of humanity. Practical, applicable technologies are desperately needed to realise a truly sustainable future.

On the one hand, carbon emissions from industry and methane emissions from agriculture are two key drivers of climate change. On the other hand, the inherent unsustainability of the petrochemical industry itself is a major roadblock to a circular economy. Significant efforts have been made to design microbiological systems to manufacture organic chemicals using biological systems, however these often rely on sugar feedstocks.  

Carbon dioxide and methane can be simply converted into microbial feedstock through electrical reduction into formic acid. This C1 compound can be consumed by formatotrophic microbes, which unfortunately are difficult to engineer to make useful products. Now, thanks to the development of synthetic biology and metabolic engineering, it is possible, though challenging, to engineer non-formatotrophic, industrial organisms to utilise formate as source of carbon and energy.  

In this project, the non-conventional, industrial yeast Yarrowia lipolytica will be engineered to both utilise formate as substrate and produce high-value products. This will be achieved by a combination of synthetic biology tools (Golden Gate, CRISPR, evolution engineering, metabolic models). In this strain design approach, it is expected to generate improved strains able to 1) tolerate high concentrations of formate 2) incorporate C1 substrates in their biomass 3) generate cellular energy and 4) produce high amount of industrially relevant products. In addition, the project will look into cell-to-cell variability in formate-based bioprocess, which is one of the current challenges of microbial biotechnology.  

This project will be based at Imperial College London.

Tumor-Targeted Delivery of Synthetic DNA Payloads By Engineered Bacteria  

  • Lead supervisor: Prof. Tom Ellis (Imperial College London)
  • Co-supervisor: Dr Teresa Thurston (Imperial College London)
  • Co-supervisor: Prof. Ramesh Wigneshweraraj (Imperial College London)

Bacteria capable of invasion into human cells offer a promising technology for cell-based therapies and could also be used to provide a route for DNA delivery, potentially enabling these bacteria to be a vector for gene therapies, DNA-based vaccines and in vivo genome engineering. Past work has demonstrated how modular DNA constructs can be used to engineer E. coli and Salmonella to target and enter cancer cell lines and tumours and specifically deliver protein payloads (e.g. toxins). The proposed project will go beyond delivery of just proteins and develop a platform for using tumor-targeting bacteria for the controlled delivery of DNA payloads that are then expressed in the host cell. We anticipate that this can become a core technology for both bacterial cell-based therapies and for DNA transfer for mammalian synthetic biology and synthetic genomics.

This interdisciplinary project will bring together the foundational synthetic biology methods of DNA-based engineering and design of synthetic expression (Tom Ellis) with cutting-edge biomedical research of intracellular host-microbe interactions (Teresa Thurston, Ramesh Wigneshweraraj). It is co-sponsored by an exciting London-based industrial partner, Prokarium, and leverages their expertise and commercial knowledge of bacterial cell therapies. The research will build on an existing synthetic biology project between the company and the London BioFoundry, but now take this in the new direction of DNA delivery.

The planned experimental work will see the student design, construct and test modular DNA programs that trigger secretion mechanisms and conjugation in relevant E. coli and Salmonella strains when these bacteria enter target cells. A core aim of this project will be to use non-pathogenic Salmonella strains as a vehicle to inject DNA encoding a eukaryotic gene into a cancer cell line. This process will be optimised and measured by tracking DNA expression and location by fluorescent imaging and single-molecule microscopy. Further work will look to test the limit of the lengths of DNA that can be transferred. Conjugation between bacteria is regularly used to transfer millions of bases of DNA in one go, and so this offers promise as a route to transfer big sections of synthetic DNA into target cells.

This project will be based at Imperial College London and is supported by Prokarium.

Design considerations for improved pDNA and therapeutics production

  • Lead supervisor: Dr Francesca Ceroni (Imperial College London)
  • Co-supervisor: Prof. Tom Ellis (Imperial College London)

Non-viral, plasmid DNA (pDNA) is the focus of great interest as therapeutic as well as a starting material for gene and cell therapies. The quality and quantity of the pDNA recovered from industrial processes is however affected by context-related impact of the plasmid, the presence of cryptic sequences, multimerisation leading to instability and non-optimal coiling. In this project we will work with AstraZeneca to consider how therapeutic plasmid sequences impact on the host cell and use engineering design rules to minimise such interactions while maximising plasmid replication stability and quality.

The constructs of interest are already in use at AstraZeneca (AZ) and we will use transcriptomic analysis and engineering control rules to re-design them in order to achieve improved quantity and quality of the pDNA while minimising impact on the host. Lab work will entail state-of-the-art molecular cloning, transcriptomic analysis and design of CRISPR-based and RNA-based feedback controllers.

This project will be based at Imperial College London and is supported by AstraZeneca.

 

Optimised construct design for in vitro and in vivo therapeutic production

  • Lead supervisor: Dr Francesca Ceroni (Imperial College London)
  • Co-supervisor: Dr Cleo Kontoravdi (Imperial College London)

In vivo delivery of therapies encoded on nucleic acids is becoming an alternative for rapid development of biologic drugs and vaccines. Nucleic acids can be delivered in viral (AAV) and non-viral forms such as plasmid DNA and mRNA. However, interactions between the therapeutic vectors and the cellular hosts can prove detrimental for the high expression levels required for efficacious effects. Here we will work closely with AstraZeneca to design and assess vector design rules to maximise sustained therapeutic production. Our aim is to understand how to successfully transfer on to industrially-relevant therapeutic systems engineering design considerations testing these in vitro and, possibly, in vivo.

The lab work will involve using Golden Gate assembly for the generation of different design configurations, transfection of these into cells and assessment of construct performance (production level) and cellular response. A model-guided approach will be adopted and will include a metabolic flux analysis model to build a pareto optimality front linking vector expression to specific cell growth rate for each design. The results will be used as a measure of process scalability and manufacturability.

This project will be based at Imperial College London and is supported by AstraZeneca.

Optogenetics for integrated, continuous processes for large-scale chemicals manufacture: Next generation manufacturing through synthetic biology

  • Lead supervisor: Prof. Nigel Scrutton (University of Manchester)
  • Co-supervisor: Dr Sam Hay (University of Manchester)
  • Co-supervisor: Prof. Eriko Takano (University of Manchester)

A major limitation of current manufacturing methods using fermentation approaches is the inability to have real-time and non-invasive, closed loop feedback control of the producing organism during long fermentations (e.g. continuous and fed-batch). The ability to monitor quantitatively product formation of volatile products in the headspace and then use this information to regulate production pathways in the host to adjust to desired levels would provide stability and predictability in manufacturing pipelines for chemicals, fuels and materials using engineering biology approaches.

 We aim to address this urgent need for volatile products whose build up in a reactor can be cytotoxic. There therefore needs to be ‘on-the-fly’ real-time control of terpene concentration and active removal of the product by on-line product capture (e.g. sparging; phase separation and related methods). We have in the Scrutton group develop downstream processing methods for active product removal but missing is the ability to capture real-time data on product levels and use of this information to offer feedback control strategies for use with the producing organisms/metabolic pathways.

We plan to achieve this using optogenetic methods where the read out of a mass spectrometer is used to regulate organisms/pathways by direct control of bioreactor LEDs for optogenetic regulation of the producing organism. If made to work this technology would be a game changer for manufacturing using Engineering Biology platforms, offering new routes to stable and predictable manufacture with real-time and non-invasive control.

The aim is to design and implement next-generation real-time monitoring and feedback control of bioproduction processes for chemicals manufacturing, using light-responsive genetic elements and enzymes. The purpose is to build a generic platform capability, using engineered production strains in the Scrutton group and the ability to rapidly engineer further in SYNBIOCHEM/FutureBRH.

This project will be based at the University of Manchester.

Engineered genetic bioaugmentation vectors and pathways for bioremediation

  • Lead supervisor: Dr Neil Dixon (University of Manchester)
  • Co-supervisor: Prof. Michael Brockhurst (University of Manchester)

Anthropogenic impact upon the environment is the biggest existential threat to humanity. Contamination of the natural environment with xenobiotics causes significant challenges in terms of containment and remediation. In these polluted environments microbial communities have been shown to evolve and adapt to grow in the presence of xenobiotics by resistance, decomposition and/or assimilation of the foreign substance. Indeed, these organisms can also provide a rich source of degradative and catabolic biosynthetic genes and pathways for use in engineered biosynthetic pathways and hosts for bioremediation.

This project will seek to use Synthetic Biology approaches to develop and optimise plasmid-based bioaugmentation strategies for bioremediation of contaminated environments. Specifically, by engineering plasmid-encoded degradative and catabolic biosynthetic pathways, for example to remove heavy metals and assimilation of plastics. This will provide novel approaches for decontamination and also provide circular economy opportunities. Alternative strategies will be employed including Adaptive Laboratory Evolution and use of Engineered Plasmids and Pathways. The evolved/engineered plasmids will then be transferred back into the indigenous bacterial community by conjugation and the impact of the modified plasmids will be studied at both the metabolic and the genetic levels. In parallel plasmid dispersal amongst the indigenous bacterial community will be studied to assess uptake, spread (horizontal genetic transfer) and longevity using genomic profiling approaches. In addition to the scientific research a key part of this PhD project will be to engage with Responsible Research and Innovation (RRI) colleagues and external stakeholders such as national and inter-governmental regulatory authorities, NGOs, and environmental pressure groups.

This PhD project will provide training in the conceptual approaches, skills and techniques of synthetic biology, plus in broad aspects of biotechnology, microbial gene expression regulation, evolutionary and environmental microbiology, molecular biology and bio-analytical methods. This project would suit individuals interested in future careers in modern environmental biotechnology, and the sustainable bioeconomy.

This project will be based at the University of Manchester.

Designing and Engineering Gamma-Butyrolactone Signalling for Synthetic Biology

  • Lead supervisor: Prof. Eriko Takano (University of Manchester)
  • Co-supervisor: Prof. Rainer Breitling (University of Manchester)

Gamma-butyrolactones are signalling molecules acting as “bacterial hormones” and regulating the production of bioactive secondary metabolites in microbial communities. They can be used to expand our ability to precisely and flexibly control engineered biological systems. This project will develop a versatile toolkit of well-characterised butyrolactone circuits for broader application in synthetic biology, building on a recently established heterologous S. coelicolor SCB butyrolactone signalling system in E. coli..

Work package 1: Design and engineer a library of diverse butyrolactone producing E. coli strains (“signalling devices”). [Pathway modification and assembly] We will modify both the chemical nature of the signals (by varying the enzymes of butyrolactone biosynthesis) and the kinetics of their production (by varying the promoter strengths and the nature of the upstream regulators of the biosynthetic pathway).

Work package 2: Design and engineer a library of diverse butyrolactone-responsive E. coli strains (“receiver devices”). [CRISPR-based protein engineering, protein structure determination] We will combine semi-targeted mutagenesis of the all butyrolactone receptor with variations in the regulatory elements to create receiver variants with a broad range of response characteristics. To complete the understanding of these receptors, protein crystallisation studies will also be conducted, which will be a first, as no known butyrolactone signal – receptor pair structure has yet been solved.

Work package 3: Quantitative characterisation of the signalling interaction between signalling and receiver devices. [LS-MS analytics, modelling] The obtained measurements will be used to parameterise an existing ensemble model of the kinetics of gamma-butryolactone signalling (Tsigkinopoulou et al. 2020).

Work package 4: Create library of E. coli integrated circuits. Based on the modelling results from WP3, selected combinations of signalling and receiver devices will be combined in a single E. coli strain to analyse a spectrum of different behaviours (bistable switch, growth-phase specific toggle switch, etc.). We will also test these designer “signalling devices” for the possibility to awaken sleeping antibiotic gene clusters.

This project provides comprehensive interdisciplinary training in methods across a range of key disciplines at the interface of biology, biosystems engineering, analytics, and bioinformatics, which are essential for the next generation of engineering biologists.

This project will be based at the University of Manchester.

 

Engineering a shape-changing light-actuated living tissue

  • Lead supervisor: Prof. Guillaume Charras (University College London)
  • Co-supervisor: Dr Andela Saric (University College London)

A long-standing challenge in bioengineering is to design tissues that can dynamically change their shapes on demand, for instance for regenerative purposes or for the development of biomimetic machines. For this, we propose to draw inspiration from embryonic morphogenesis when tissues undergo a series of dramatic shape changes to generate a complex organism. These are driven by spatiotemporal gradients of tension generated by the cytoskeleton and controlled by molecular switches called RhoGTPases.

In turn, the activity of RhoGTPases arises from spatial patterns in the expression of genes encoding their regulators, RhoGEFs and RhoGAPs. RhoGEFs activate RhoGTPases leading to enhanced activity of myosin motors and tension, while RhoGAPs downregulate RhoGTPase activity to decrease tension. Many complex cellular morphogenetic events, such as mitotic morphogenesis, are controlled by combinations of RhoGEFs and RhoGAPs acting in different subcellularpatial locations to create the steep spatiotemporal tension gradients that lead to shape change. At the tissue scale, similar processes are at play with groups of cells coordinating their contractile and migratory behaviours to generate thelead to spatiotemporal gradients in tissue tension that drive embryonic morphogenesis.

Our goal is to harness the RhoGTPase signalling pathway to create a shape-shifting living tissue that can be controlled by light, inspired by the design rules observed during embryonic morphogenesis. We will focus on two aims. First, we will design molecular actuators controlling cell mechanics based on optogenetics with one actuator increasing contractility (based on a RhoGEF) and the other decreasing contractility (based on a RhoGAP). We will then characterise their effects on cell and tissue mechanics at minute to hour time-scales. In the second aim, we will integrate these data into a computational framework that combines the theory of elasticity for tissues and evolutionary algorithms. The computational framework will suggest spatiotemporal actuation patterns to reach any desired tissue shape and we will implement these in experiments. We will focus in particular on synthetically replicating morphogenetic changes observed during embryonic development.

This project will be based at University College London.

Stochasticity-resilient control of microbial communities in bioprocessing

  • Lead supervisor: Dr Duygu Dikicioglu (University College London)
  • Co-supervisor: Prof. Gary Lye (University College London)

Cooperation and competition between microbial species that share the same environment drive niche-specialisation and higher-level community organisation. In contrast to natural microbial communities, which have been used in biotechnology processes, including fermentation, waste treatment, and agriculture, for millennia, synthetic microbial communities are well-defined and have reduced complexity. Engineered communities are increasingly finding their way into diverse biotechnological applications, including the bioproduction of medicines, biofuels, and biomaterials from inexpensive carbon sources. Microbial biotechnology benefits from consortia due to the unique catalytic activities of each member, their ability to use complex substrates, compartmentalization of pathways, and distribution of molecular burden. Furthermore, the construction of the microbial consortia is enhanced by computational models through the prediction of preferred metabolic cross-feeding networks and inference on population dynamics over time.

Recent work on perturbations on microbiomes demonstrated that many dynamic transitions follow stochastic rather than deterministic paths, and therefore result in shifts to/from unstable and highly variable community states. The term the ‘Anna Karenina principle’ was coined to describe this argument, based on the quote from Leo Tolstoy that “all happy families look alike; each unhappy family is unhappy in its own way.” This notion highlights a major obstacle in the successful utilisation of microbial communitites in well-controlled bioprocess settings.

This project aims to address the above stated challenge by discovering metabolic identifiers that withstand the stochastic variations in synthetic community structures, which will allow robust and tuneable control in a bioprocess setting. Community metabolic networks will first be investigated by stochastic metabolic modelling; the candidate metabolic markers identified by modelling will then be used to design a platform for monitoring metabolic markers during growth. The high-throughput platform will allow sufficient variability in community structures to monitor the response to stochasticity. Promising named markers will then be used to implement control actions for a benchtop fermentation process that is designed for the synthetic community. The analyses will be carried out on synthetic (i) mixed bacterial and yeast communities of suspended cells, and (ii) mixed bacterial communities of immobilised cells in biofilms. The analysis of different community structures will inform on the generalisability of the findings.

Our goal is to harness the RhoGTPase signalling pathway to create a shape-shifting living tissue that can be controlled by light, inspired by the design rules observed during embryonic morphogenesis. We will focus on two aims. First, we will design molecular actuators controlling cell mechanics based on optogenetics with one actuator increasing contractility (based on a RhoGEF) and the other decreasing contractility (based on a RhoGAP). We will then characterise their effects on cell and tissue mechanics at minute to hour time-scales. In the second aim, we will integrate these data into a computational framework that combines the theory of elasticity for tissues and evolutionary algorithms. The computational framework will suggest spatiotemporal actuation patterns to reach any desired tissue shape and we will implement these in experiments. We will focus in particular on synthetically replicating morphogenetic changes observed during embryonic development.

This project will be based at University College London.