Leverhulme Centre for Cellular Bionics Studentships

The Centre for Cellular Bionics is training a new generation of PhD graduates in the emerging field of Cellular Bionics to explore the science of fusing the living and non-living, transforming bioengineering and design.

Leverhulme Cellular Bionics Studentships Starting 2019

Advancing bacterial 3D printing for the production of next-generation bio-materials

Funded by the Leverhulme Doctoral Scholarship Programme in Cellular Bionics – 3 year PhD studentships - APPLY HERE

Supervisors: Dr Guy-Bart StanDr John HeapDr Connor Myant

Natural and engineered bacteria possess extraordinary biosynthetic capabilities. These can serve almost any application imaginable: from functionalised bacterial cellulose patches for antimicrobial wound dressing to bacterial self-healing concrete or the use of bacteria to produce nacre-inspired composite materials. The ability to harness such great manufacturing potential into customised designs with defined three-dimensional shape and composition remains, however, largely elusive.

Current 3D bacterial printing approaches rely on the use of scaffolds or conventional layer-by-layer additive manufacturing strategies to shape their designs, often resulting in unsophisticated structures with restricted geometries and monotonous physico-chemical and mechanical properties. In contrast, one-body yet heterogeneous composite materials with seamless transitions between disparate properties (functionally graded composite materials) have long been a holy grail for designers and engineers.

This project will employ a new 3D printing method, developed by the project supervisors, that is merging the fields of synthetic biology and 3D Printing. 3D Printing has enabled the creation of complex geometric structures previously unavailable to design engineers and scientists. However, this vast new pallet of object geometries has been limited to non-living materials. The ability to create bespoke biological structures directly from a 3D printing process has so far eluded us. The focus of this project is to challenge this limitation and open a new era of 3D bio-printing.

More specifically, this project will develop a novel 3D printing process that employs nature as the 3D printer, at a cellular level; whilst utilising engineering’s ability for highly accurate spatial control. It will build on ongoing efforts to bridge the gap between synthetic biology and 3D printing technology and will focus on further developing the necessary biological tools for the effective manufacturing of bio-materials in 3D. In the initial phases of the project, less-sophisticated, simple proof-of-concept structures will be generated. This will help identify and delimit expected and also unexpected challenges for the production of more complex composite materials. Next steps will include, but not be limited to, optimisation of biosynthetic pathways in the working chassis; finding appropriate external 3D control strategies to improve printing efficiency and accuracy; incorporation of biomolecular feedback control into genetic designs; development of efficient secretion systems and alternative “secretion” strategies (e.g. enzyme display for extracellular biosynthesis of one or more constituents of the composite material); bio-material engineering (e.g. through incorporation of bacterial amyloids) and functionalisation (e.g. silver nanoparticles); development and integration of mathematically-modelled gene expression systems into 3D printing software for true computer-guided bio-fabrication; etc. Finally, resultant next-generation 3D bio-materials will be analysed for their physico-chemical and mechanical behaviour and compared with existing bio-materials.

The successful development of this bio-printing technology could have significant impact in the medical field, biotechnology, and pharmaceutical industries. From the development of high throughput pharmaceutical screening equipment to 3D microfluidics and novel biomaterials. In addition the 3D printing technique offers a new paradigm in 3D manufacturing applications were the printing process is not limited to 2D planar layer stacks but rather a true 3D object.

The ideal candidate will have a background in some of these areas: bacterial synthetic biology (e.g. E. coli), genetic engineering, optogenetics, metabolic engineering, biomolecular feedback design and implementation, modelling in biology, computational modelling

The project will bring together a truly multidisciplinary team of synthetic biologists, bioengineers, and design engineers. The work will be support by a parallel project run by the supervisors; Dr Guy Bart Stan from the Department of Bioengineering, Dr John Heap from the Department of Life Sciences, and Dr Connor Myant from the Dyson School of Design Engineering. If you have any questions regarding the application please email Dr Guy-Bart Stan (g.stan@imperial.ac.uk).

On-site assembly of the actin cortex in semi-synthetic cells to control cell mechanics and behaviour

Funded by the Leverhulme Doctoral Scholarship Programme in Cellular Bionics – 3 year PhD studentships - APPLY HERE

Supervisors: Dr Elani YuvalDr Nick BrooksDr Marina Kuimova

Can we engineer semi-synthetic cells that can alter their global mechanical properties on-demand, in response to external stimuli? Can we link these mechanical properties to downstream protocellular ‘behaviours’ that are relevant to therapeutic and biotechnological applications? This project aims to address these questions using a cellular bionics approach. By intermingling both biological and synthetic components, an actin cortex will be manufactured/disassembled within vesicle-based synthetic cells in response to light of defined wavelengths. This will allow the synthetic cell to dynamically switch between mechanically distinct states (i.e. different rigidities and viscosities). Coupling cell biomechanics to different behaviours, in this case the cell’s ability to squeeze through constrictions under flow, will be investigated using a microfluidic device. This project will first require an understanding of the effect of the actin cortex on cell mechanics to be developed using molecular rotors and flickering analysis. These insights will then allow us to controllably engineer the stimuli-responsive systems. 



A synthetic biology toolbox for electronic control of gene expression

Funded by the Leverhulme Doctoral Scholarship Programme in Cellular Bionics – 3 year PhD studentships - APPLY HERE

Supervisors: Dr Thomas OuldridgeDr Danny O'HareDr Rodrigo Ledesma

The 20th Century was characterized by the growth of a myriad of technologies based on digital electronics. Engineering of biological systems has the potential to be similarly revolutionary in the 21st Century. Before this dream can be realized, however, precise, programmable control of complex biological systems needs to become simpler, and the interface with other engineered technologies needs to be made more robust. In this project, the student will develop a modular system for interfacing electronic signals with engineered cells. The proposed mechanism utilizes electrochemical oxidation and reduction of redox molecules at electrodes, and the subsequent activation of redox-sensitive transcription factors in the vicinity of those electrodes. The electrogenetic module will allow implementation of precise spatio-temporal control of biological systems from a smartphone or personal computer, with applications in bioproduction, biomaterials, biosensors, diagnostics and more.  

SolarBioChip: development of a solar bio-battery for printed bioelectronics

Funded by the Leverhulme Doctoral Scholarship Programme in Cellular Bionics – 3 year PhD studentships - APPLY HERE

Supervisors: Prof Milo ShafferProf Peter Nixon | Prof Klaus Hellgardt

We have recently described the development of a printed cyanobacterial biobattery with potential application as a biodegradable power supply for low-power devices including biosensors and printed bioelectronics (Sawa M, Fantuzzi A, Bombelli P, Howe CJ, Hellgardt K & Nixon PJ (2017) Electricity generation from digitally printed cyanobacteria. Nature Commun. 8, 1327). The biobattery is conveniently fabricated by a scalable inkjet method to print both cyanobacterial cells and carbon nanotube electrode surfaces on which the cells grow as a biofilm. In the light the printed device acts as a biophotovoltaic cell producing electrical current from electrons released from the cell during photosynthetic electron transport. Importantly, the biobattery can also produce electricity in the dark from the breakdown of stored products of photosynthesis, such as carbohydrate. The aim of this project is to improve the power output of the first-generation solar biobattery so that it can meet the power requirement for use in ultra-low-power microprocessors, which will be undertaken in collaboration with Arm Ltd. Areas for investigation include the development of novel cyanobacterial strains (Nixon), the testing of novel electrode materials for improved conductance and biocompatibility (Shaffer), the development of robust printing techniques and composite design (Hellgardt) and the testing of printed biobattery on powering an ultra-low-power Arm processor in collaboration with Arm Ltd. Ultimately, we aim to fabricate a semi-living electronic device powered by sunlight using cyanobacterial cells – the ‘solarbiochip’.

Synthetic Extremophiles: Cellular bionics for extreme conditions

Funded by the Leverhulme Doctoral Scholarship Programme in Cellular Bionics – 3 year PhD studentships - APPLY HERE

Supervisors: Dr Nick BrooksProf Oscar CesProf Rob Law 

One of the key markers of life is its ability to adapt and evolve in response to its surroundings, helping organisms to survive in their ecological niches. Such adaptations can be structural, behavioural or physiological. In the case of extremophiles this trait extends to enabling life to thrive in forbidding environments that were once not thought to be able to sustain life: from extremes of pressure all the way through to extremes of temperature. This studentship aims for the first time to generate biological-synthetic hybrid systems that are capable of surviving extremes of pressure (equivalent to being at the bottom of the Mariana Trench, the deepest ocean point in the world; >1000atm)-synthetic extremophiles. By fusing living and non-living systems we will generate ensembles that are able to modify their composition and make-up in response to external changes in hydrostatic pressure. This has the potential to transform our understanding of how molecular components come together to introduce emergent behaviour. In addition, it will lead to the manufacture of biological components that are ideally suited to a wide range of industrial, biotechnical and consumer applications where performance under extreme conditions and the capability to respond to extreme operating conditions are fundamental prerequisites.

*Engineering novel cell mimetic membrane architectures

*this is a Chemistry departmentally funded studentship (i.e. not funded through the Leverhulme Trust), but the awardee will join the Cellular Bionics and ICB CDT cohorts and bespoke training oportunities. Please apply directly to Imperial Gateway

Supervisors: Dr Yuval ElaniProf John Seddon 

Cell mimicry – the ability to imitate the physical architecture, function and behaviour of cells – is proving to be an increasingly useful conceptual framework in (i) furthering our understanding of biological systems and (ii) constructing novel bio-inspired devices for clinical and industrial applications. The ability to generate membrane-based structures is proving to be especially powerful in both respects. However, the field has reached an impasse: although plasma membrane mimics are well established, mimics of alternative membrane structures are lacking. In this project, a suite of droplet-based technologies to assemble, manipulate, and functionalise synthetic analogues of a repertoire of membranous motifs — including fusogenic exosomes, synapses, and double membranes — will be developed, and their biophysical properties characterised. The use of these structures as functional components in vesicles microreactors and synthetic tissues will be explored.  This project will lead to a step change in our ability to generate Synthetic Biology systems from the bottom up, allowing us to reproduce features associated with intra-cellular compartmentalisation and inter-cellular communication. This project is multidisciplinary, incorporating elements of chemical biology, microfluidics, biophysics and biointerface science.

For further information please contact Yuval at y.elani@imperial.ac.uk