Projects for the 2019 cohort

The Cellular Bionics Projects for entry October 2019 are listed below and we invite applications. These are 3 year PhD studentships funded by the Leverhulme Doctoral Scholarship Programme.  Please follow the directions here when applying and check the eligibility criteria.

Studentships 2019 - Apply Now

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. 



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

Projects from the 2018 cohort

Studentships starting 2018

Engineering biointerfaces between synthetic and biological cells

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

Supervisors: Dr Yuval Elani |  Dr Karen PolizziProfessor Oscar Ces

One of the central ideas behind cellular bionics is that cell functions can be augmented both by introducing non-biological components into cells, and by interfacing cells with functionalised soft-matter microsystems. To date, most efforts have focused on engineering isolated self-contained systems. The design of higher order systems, where discrete units are physically linked together in a network, are in turn expected to yield higher-order functions (akin to how cells function as a collective within tissues).  Doing this requires the development of novel biophysical and chemical toolkits. Recently, we have developed a new approach to assemble, manipulate and selectively fuse synthetic cell-mimetic vesicle networks, exploiting optical tweezers, membrane biophysics, and nanoparticle conjugation. In this project, these techniques will be used to generate tissue-like 2D and 3D artificial cell networks as well as architectures that mimic cell-cell interfaces (synapses, gap junctions, etc.). Technologies to construct hybrid living/synthetic proto-tissues composed of interlinked biological and artificial cells will be developed, and methods to shuttle material between the biological and synthetic nodes explored. This project will lead (i) to the development of new classes of biomaterials and (ii) to new tools to biochemically manipulate cells for a better understanding of cell biology.

Development of next-generation Bio-Printing

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

Supervisors: Dr Connor Myant Dr Guy-Bart StanDr John Heap

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 alluded us. Current Bio-Printing methodologies are limited to the creation of cell cultures and scaffolds that allow cellular material to grow within them to create tissue-like structures. These simple materials lack sophistication, are non-functionalised and are reliant on the scaffold to determine mechanical properties. As yet, 3D printing has not been able to match nature's ability to create such structures. The focus of this project is to challenge this limitation and open a new era of bio-printing.

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 through put 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.

This project will employ a novel 3D Printing process that employs nature as the 3D printer, at a cellular level; whilst utilizing engineering's ability for highly accurate spatial control. It is a true cellular-bionic 3D printing process. This project will focus on developing the advanced optical methods needed to control the light signals employed during the printing process. The project will bring together a truly multidisciplinary team of design engineers, mechatronics, bio-engineers and synthetic biologists. The work will be support by a parallel project run by the supervisors; Dr Connor Myant from the Dyson School of Design Engineering, Dr Guy Bart Stan from the Department of Bioengineering, and Dr John Heap from the Department of Life Sciences. If you have any questions regarding the application please email Dr Connor Myant.

Requirements:

  • You must have a MEng or MSc degree (or equivalent experience and/or qualifications) in an area pertinent to the research topic, i.e. Engineering, Physics, Chemistry or similar.
  • A strong track record, or interest, in mechatronics, robotics or optics is desirable.
  • Be prepared to work within a multidisciplinary research group
  • You must have a high standard undergraduate degree at 1st class or 2nd upper class level (or international equivalent).
  • You must meet Imperial’s English standards.
  • You must have excellent communication skills and be able to organise your own work and prioritise work to meet deadlines.
  • Any published scientific papers would be a plus.

Functionally optimized biofilms for building façades and architecture

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

Supervisors: Professor Peter Childs | Dr Connor MyantDr Laura Barter

Building façades remain one of the most important exterior elements for the functionality of a construction. While the façade can be an elegant component that helps to define the unique architectural aesthetics of the building, it also has critical roles such as building protection, energy performance and interior function of a building. As technology continues to improve, different options for improvement become available for incorporation into building facades. An exciting avenue for novel building facades is the use of bio-materials or bio-receptive materials that incorporate, and harness, living systems to improve façade performance.

Building exteriors are an underutilized canvas that could provide a rich environment for cellular bionic systems in the following means: protection of building surfaces from weathering, the cleaning and repairing of exterior surfaces, the control of indoor temperatures and comfort, and by providing smart fire defences.  In addition, cellular bionic building facades present an opportunity to create something delightful such as colourful designs that alter appearance and adapt with their surroundings, the weather and changing fashions. This project presents a novel definition of “smartness”, one that harnesses the embodied intelligence of bacterial organisms and their biofilms. Bacteria can react to novel stimuli in real-time, reproduce and self-repair as well as learn behaviour according to environmental circumstances. The possibility that we may create bio-facades that can communicate to their user, provide feedback and adapt to their environment proposes an initial step towards an exciting vision of the smart city of the future.

This project will investigate the potential use of bio-receptive materials capable of growing microorganisms directly onto their surface as novel cladding systems. This system will go beyond the current limitations of green walls, with the accompanying need for mechanical irrigation systems and expensive maintenance, and design cellular symbiotic systems that feed off their surrounding environment. Instead of building against nature, biological materials and processes will be integrated into structurally engineered materials and processes. By designing surfaces that are bio-receptive we will carefully select and grow bio-films that perform a desired function actively delivering a beneficial system. 

Supervision:

The project will be supervised by Professor Peter Childs and Dr Connor Myant from the Dyson School of Design Engineering, and Dr Laura Barter from the Department of Chemistry. If you have any questions regarding the application please email Dr Connor Myant or email Professor Peter Childs.

Requirements:

  • You must have a MEng or MSc degree (or equivalent experience and/or qualifications) in an area pertinent to the research topic, i.e. Biology, Chemistry, Material Science, or Engineering.
  • You must have a high standard undergraduate degree at 1st class or 2nd upper class level (or international equivalent).
  • You must meet Imperial’s English standards.

Organelle breeding for artificial cells

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

Supervisors: Dr Nick Jones | Professor Patrick Chinnery (Mitochondrial Biology Unit, Cambridge)

Recent research indicates that healthy cells can donate their power-stations (organelles, called mitochondria) to sickly ones. This has led to the idea of ‘mitochondrial transplants’: using the bulk delivery of these organelles for therapeutic purposes. Bulk breeding/generation of mitochondria or chloroplasts could also be used for future artificial cells they might power. This would involve modifying cells or using artificial cells to breed large numbers of organelles. As each organelle has its own genome, each can evolve and mutate. This evolution can involve large-scale deletions of the mitochondrial genome which can disable mitochondria as power-stations and even turn them into power-sinks. Any bulk production of organelles must be acutely sensitive to their mutational profile. Tracking the evolving quality of thousands of power-stations inside millions of, possibly replicating, quasi-living systems will require the development of new theoretical tools to infer the evolutionary structures these cells display that exploit modern sequencing technologies. The student will develop these in collaboration with Nick Jones (Imperial Mathematics), members of the mitochondrial biology unit in Cambridge and as part of the wider Leverhulme centre in cellular bionics in Imperial.

Cells and organelles as embedded biomodules in artificial cells

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

Supervisors: Dr Yuval Elani | Dr Laura BarterProfessor Oscar Ces

The bottom-up construction of artificial cells is becoming ever more advanced, with vast applications for their use as biomimetic micromachines that can perform chemically and biologically relevant tasks. Traditionally, molecular-level approaches are used, where selected biomolecules (DNA, lipids, proteins) are assembled into a cell-like entity. In this project, building on previous work (Elani et al. Sci. Rep., 8; 4564, 2018) a new conceptual framework will be explored. In addition to biomolecules, whole biological structures — including engineered cells and chloroplasts — will be commandeered and embedded within synthetic cells, allowing them to serve modular functions as part of a hybrid entity. Hijacking ‘living’ modules will allow us to leverage the power of cell-biology to confer, for example, battery, sensor, and reactor functionalities into artificial cells. This project will involve the development of novel microfluidic technologies for hybrid artificial cell construction, and the exploration of the engineering principles needed to physically and biochemically couple the synthetic and biological modules together.