Biological Sciences

PhD Projects

The listing below is for projects which are currently recruiting students. The majority of these are advertised in autumn and filled in January-March the following year. However we often have funded projects available outside this period, so please check back regularly.

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Project Titles

Supervisor Topic
Dr Manfred Auer *EPSRC* Validating “undruggable†or orphan cancer targets by combining fragment based screening peptidomimetic chemistry, structural biology and cell biology
Dr Atlanta Cook Structural studies on RNA editing enzymes in Trypanosoma brucei
Dr Atlanta Cook How fungi manage stress: the role of RNA binding proteins in post-transcriptional adaptations to heat shock
Dr Andrew Free *MRC DTP* Antimicrobial Resistance Gene Persistence in Wastewater Treatment Systems, the Natural Environment and Patient Samples in the Lothians.
Prof Maurice Gallagher Role of Cold Shock Proteins in eliciting plant defence
Dr Ramon Grima Stochastic modelling of cell movement and cell-cell interactions in cell populations
Dr Ramon Grima *EPSRC* Developing realistic mathematical models of cell movement and interaction
Dr Louise Horsfall Exploring bacterial nanoparticle biosynthesis with synthetic biology
Dr Julia Richardson DNA repair mechanism and inhibition of Tdp1
Dr Julia Richardson Developing Transposon Tools for DNA integration
Prof Susan Rosser Cell engineering strategies to enhance production of next-generation biologics
Prof Peter Swain The role of memory in cellular decision-making and fitness
Prof Peter Swain A whole-cell model to predict changes in translation and growth during cellular stress
Prof Peter Swain A whole-cell model to predict the energetic costs imposed by synthetic constructs
Dr Stephen Wallace *EPSRC* A Synthetic Biology Approach Towards the Bio-production of Medicinally-relevant Natural Products
Dr Baojun Wang Synthetic biology-enabled new generation biosensors for global health and environment challenges
Dr Baojun Wang Programmable precision guided bacteriophages for selective killing of AMR gut pathogens
Dr Baojun Wang Genetic programs for advanced cellular information processing and behaviour control
Dr Baojun Wang *EPSRC* Synthetic biology-enabled new generation biosensors for global health and environment challenges

Project Details

*EPSRC* Validating “undruggable†or orphan cancer targets by combining fragment based screening peptidomimetic chemistry, structural biology and cell biology

Description:

Supervisors: Dr Manfred Auer (Manfred.Auer@ed.ac.uk) and Dr Jeyaprakash Arulanandam Arulanandam@ed.ac.uk)

Application deadline – 14 March 2018

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

In comparison to prominent and successful target classes like GPCRs, the success rate in targeting protein – protein interactions (PPIs) is very low. The identification of chemical starting points in the initial phases of the hit and lead discovery process is often very limited. PPIs comprise highly diverse interactions which are often characterized by structural flexibility, high affinity, and large surface areas. The pharmaceutical industry is therefore cautious and hesitant to perform high throughput screens costing upwards of 1 million dollars on a PPI unless it is a fully validated drug target. This translates to around 50% of all human cancer-causing genes being missed. Target validation involves 2 aspects. (a) Biological validation, (b) Chemical validation, which involves the identification of a proven binding and inhibitory reagent, stopping function in biochemical, cellular and potentially model organism assays.  The suggested project aims at the establishment and exemplification of a generic process for chemical validation of proteins without known function which could represent important new targets in cancer drug discovery. Tentatively, these include i) Survivin (a key component of the Chromosomal Passenger Complex essential for error-free cell division), ii) the Chromosomal Passenger Complex (consists of Borealin, Survivin, Aurora B and INCENP), iii) the Ska complex (consists of Ska1, Ska2 and Ska3) essential for the mitotic spindle driven chromosome segregation and iv) CENP-32, an RNA methyltransferase implicated in maintaining the intact mitotic spindle assembly.

Step 1: Development of dimer, trimer and tetramer peptidomimetic libraries which contain one fluorinated aromatic amino acid by split & mix solid phase chemistry.

These libraries will include, as building blocks, linear and cyclic amino acid derivatives which vary in stereochemistry, in side chains and in distance between acid and amine functionality (beta/gamma amino acids) allowing for an enormous diversity to tackle PPIs.

Step 2: identification of a molecule which binds to the target.

Libraries will be cleaved from microbeads and initially tested for target binding in mixtures of limited complexity. Two of the established screening platforms of the Auer lab will be applied (see website).  

Step 3: Optimizing hit affinity by iterative synthesis, affinity determination and structural biology.  Our biophysical methods allow following the concept of fragment based screening and the identification of low affinity binders in the mM KD range. Applying miniaturized OBOC chemistry [1], a variety of label free and fluorescence single molecule assay techniques [2], and structural methods, micromolar to nanomolar binders will be developed.

Step 4: Functional evaluation of target modulation in cellsAffinity optimized peptidomimetic hits will be tested for functional activity in cellular assays within the JP lab in unlabelled and fluorescently labelled forms. Single molecule and super resolution imaging will be applied using excellent microscopy equipment in the Auer lab and the WTCCB facility.

A chemist with broad interest in biophysics, screening, structural biology and imaging and with a dedication to progress cancer translational biology will be required for this strongly interdisciplinary project. The completion of this PhD project will provide the candidate with excellent chances to progress a career in translational science.  

Auer Lab website: http://auer.bio.ed.ac.uk/JP Lab website: http://jeyaprakash.bio.ed.ac.uk

 

Further Information:

This project is eligible for EPSRC funding and is open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) Deadline for applications: 14 March 2018

References:

[1]    Hintersteiner M, Kimmerlin T, Kalthoff F, Stoeckli M, Garavel G, Seifert JM, Meisner NC, Uhl V, Buehler C, Weidemann T, Auer M, (2009) A single bead labelling method for combining confocal fluorescence on-bead screening and solution validation of tagged one bead one-compound libraries. Chemistry & Biology 16(7), 724-35.doi:10.1016/j.chembiol.2009.06.011, PMID: 19635409.[2]    Meisner NC, Hintersteiner M, Müller K, Bauer R, Seifert JM, Naegeli HU, Ottl J, Oberer L, Guenat C, Moss S, Harrer N, Woisetschläger M, Bühler C, Uhl V, Auer M (2007) Identification and mechanistic characterization of low molecular weight inhibitors for HuR. Full Article. Nature Chemical Biology; 3 (8):508-15. doi:10.1038/nchembio.2007.14, PMID: 17632515.[3]    Jeyaprakash AA, Klein UR, Lindner D, Ebert J, Nigg EA and Conti E.  Structure of a Survivin-Borealin-INCENP Core Complex Reveals How Chromosomal Passengers Travel Together. Cell (2007) 131, 271-285.[4]    Abad MA, Medina B, Santamaria A, Zou J, Plasberg-Hill C, Madhumalar A, Jayachandran U, Redli PM, Rappsilber J, Nigg EA and Jeyaprakash AA. Structural Basis for Microtubule Recognition by the Human Kinetochore Ska Complex. Nat Commun (2014) Jan13; 5:2964. Doi:10.1038/ncomms3964.

Subject Area(s):

Synthetic Organic Chemistry, Biochemistry, Bioinformatics, Biophysics, Cancer/Oncology, Cell Biology/Development, Medical Imaging, Molecular Biology, Structural Biology

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Structural studies on RNA editing enzymes in Trypanosoma brucei

Description:

Supervisors:  Dr Atlanta Cook (atlanta.cook@ed.ac.uk) and Dr Achim Schnaufer (achim.schnaufer@ed.ac.uk)

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

Trypanosomatid parasites account for a number of neglected tropical and livestock diseases and present a huge health and economic burden in many developing countries. These organisms have a distinctive, essential RNA editing pathway, known as uridine deletion/insertion editing. During editing, mitochondrial mRNAs are recoded using small guide RNAs (gRNAs) that anneal to mRNA sequences and direct cleavage; insertion and/or deletion of U bases; and re-ligation at specific sites. Core enzymatic activities associated with editing are found in 20S editosome complexes, which coordinate with other mRNA processing enzymes to deliver edited, mature mRNAs to the ribosome. Key questions that we wish to address are how editosomes use RNase III enzymatic activity, usually associated with double stranded RNA cleavage, to cut only the mRNA strand and how mRNA strands at edited sites are subsequently ligated together.

This is an interdisciplinary project between and the Cook and Schnaufer labs. The student will undertake biophysical, biochemical and structural studies on enzymes involved in trypanosomal RNA editing and use information from these studies to generate functional hypotheses that can be tested in the organism. The main methodologies used will be protein purification and biochemical characterization; RNA biochemistry; X-ray crystallography; biophysical characterization e.g. surface plasmon resonance, isothermal titration calorimetry; trypanosomatid culture and characterization

This project will be joint supervised by Atlanta Cook and Achim Schnauferhttp://www.wcb.ed.ac.uk/research/cookhttp://schnauferlab.bio.ed.ac.uk/http://cook.bio.ed.ac.uk/

 

Further Information:

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply  If you would like us to consider you for one of our scholarships you must apply by 12 noon on Monday 5th January 2018 at the latest.

References:

Panigrahi, A.K., Ernst, N.L., Domingo, G.J., Fleck, M., Salavati, R. and Stuart, K.D. (2006) Compositionally and functionally distinct editosomes in Trypanosoma brucei. RNA, 12, 1038-1049.

Schnaufer, A., Wu, M., Park, Y.J., Nakai, T., Deng, J., Proff, R., Hol, W.G. and Stuart, K.D. (2010) A protein-protein interaction map of trypanosome ~20S editosomes. J Biol Chem, 285, 5282-5295.

Carnes, J., Trotter, J.R., Ernst, N.L., Steinberg, A. and Stuart, K. (2005) An essential RNase III insertion editing endonuclease in Trypanosoma brucei. Proc Natl Acad Sci U S A, 102, 16614-16619.

Trotter, J.R., Ernst, N.L., Carnes, J., Panicucci, B. and Stuart, K. (2005) A deletion site editing endonuclease in Trypanosoma brucei. Mol Cell, 20, 403-412.

Kang, X., Gao, G., Rogers, K., Falick, A.M., Zhou, S. and Simpson, L. (2006) Reconstitution of full-round uridine-deletion RNA editing with three recombinant proteins. Proc Natl Acad Sci U S A, 103, 13944-13949.

Subject Area(s):

Protein and RNA biochemistry, Structural Biology, Parasitology

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How fungi manage stress: the role of RNA binding proteins in post-transcriptional adaptations to heat shock

Description:

Supervisors:  Dr Atlanta Cook (atlanta.cook@ed.ac.uk) and Dr Edward Wallace

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

Fungal pathogens are a major worldwide health burden, killing more people each year than malaria or tuberculosis. However, fungal pathogenesis and, in particular, how fungi adapt to human hosts at the start of infection, is poorly understood. On infecting their host, fungal pathogens are subject to stresses, such as heat shock, which they have to adapt to in order to grow and cause disease. We have recently characterized massive changes in RNA-protein interactions during heat shock, and are investigating how these changes allow cells to survive stress. We hypothesize that conserved RNA binding proteins (RBPs) are early responders in stress adaptation and that rapid change in post-transcriptional control of mRNAs by RBPs allows a rapid alteration of the proteome.

This project is a mixture of lab-based molecular biology and computational studies that will use quantitative, time-resolved methods to study changing populations of mRNA bound to RBPs. Using rapid cross-linking and cDNA analysis (CRAC) the student will generate RNAseq libraries that will give high resolution datasets (in time and sequence space) of changing RNA-protein interactions over the course of heat stress in budding yeast. These findings will give a mechanistic insight into stress adaptation that can be extended to pathogenic fungal models. There will be opportunities to integrate structural data on RNA-protein complexes, arising from studies in the Cook group. Finally, the data sets will be used to inform mathematical models of stress adaptation that can give systems level insights into mechanisms of fungal stress responses.

The successful candidate will be enthusiastic about combining experimental (yeast genetics, RNA and protein biochemistry) with computational (bioinformatics, statistics, quantitative modeling) methods.

Further InformationThis project will be joint supervised by Atlanta Cook and Edward Wallacehttp://www.wcb.ed.ac.uk/research/cookhttp://cook.bio.ed.ac.uk/

https://scholar.google.co.uk/citations?user=7FLIJBAAAAAJ&hl=en

 

Further Information:

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply  If you would like us to consider you for one of our scholarships you must apply by 12 noon on Monday 5th January 2018 at the latest.

 

References:

Reversible, Specific, Active Aggregates of Endogenous Proteins Assemble upon Heat Stress. Wallace, et al., Cell 2015. doi:10.1016/j.cell.2015.08.041

Stress Adaptation. Brown, et al., Microbiol Spectr 2017. doi:10.1128/microbiolspec.FUNK-0048-2016Protein-RNA interactions: new genomic technologies and perspectives.

König, et al., Nat Rev Genet 2012. doi:10.1038/nrg3141

Subject Area(s):

Quantitative transcriptomics, RNA-protein interactions, fungal infection

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*MRC DTP* Antimicrobial Resistance Gene Persistence in Wastewater Treatment Systems, the Natural Environment and Patient Samples in the Lothians.

Description:

Supervisors: Dr Andrew Free (andrew.free@ed.ac.uk)   Prof. Rosalind Allen

Application deadline - 10 January 2018

Interested individuals must follow the "how to apply" link on the Precision Medicine web page: https://www.ed.ac.uk/usher/precision-medicine/how-to-apply

relevantmicroorganisms constitutes a current global health challenge. Genes encoding AMRoriginate in the natural environment, but can be selected for and proliferate in clinicalsituations and in engineered wastewater treatment (WWT) plants, which often containsignificant levels of common antibiotics. Understanding factors which affect the proliferationand survival of AMR genes in both WWT plants and the natural environment would allow us todevelop new strategies to control these reservoirs of AMR which provide the source of AMRresistantmicroorganisms in patients.Previous work, including our own analysis of data from replicate lab-scale WWTreactors, shows that the microbial species composition of WWT reactors can fluctuate suddenlyand stochastically over time, leading to large changes in the microbial ecology of the system.Such ecological transitions have the potential to alter dramatically the competitiveness andpersistence of bacteria encoding AMR in the system, and could be triggered in full-scalesystems by changes in the operating conditions, waste influx or process instability. Suchtransitions would lead to an altered potential for release of AMR genes and organisms into thenatural environment over time.Here, we will study the effect of microbial community instability on AMR genepersistence in lab-scale reactors, full-scale WWT plants and the surrounding environment overtime, helping us to understand, and eventually model and control, these effects. We willbenchmark our studies via the quantification of the same AMR genes in locally-acquired faecalsamples from healthy, dysbiotic and antibiotic-treated patients.The previous work of the supervisors in studying community variation in replicated labscalesystems gives us ready access to the molecular, bioinformatic and statistical techniquesrequired for this analysis. We have also previously developed mathematical models of variationin these systems, and of de novo evolution of AMR in various contexts. Our contacts in thewastewater treatment, environmental and clinical sectors give us access to samples,methodologies and datasets which will assist with the parts of the study conducted outside thelaboratory setting.

Aims• To develop and optimise PCR-based assays for common classes of AMR genes (tetracycline,erythromycin, chloramphenicol, sulphonamide, b-lactam and gentamycin resistance) usingprimers and protocols provided by the James Hutton Institute.• To set up and sample replicate lab-scale WWT reactors over time to determine changes inmicrobial community composition (using metataxonomic approaches based on 16S rRNAgenes) and AMR gene abundance using the optimized PCR assays.• To monitor fluctuations in microbial community composition and AMR gene abundance in afull-scale WWT plant and the surrounding environment over time, and correlate observedchanges with alterations in the operating parameters, process efficiency, and potentialchemical stressors in the plant.• To compare AMR gene occurrence in full- and lab-scale WWT reactors with that in a preexistingset of locally-acquired faecal samples from healthy and dysbiotic patients with orwithout previous antibiotic treatment. These samples are available in the Free lab.

Training outcomes• Development of molecular skills used for the analysis of gene and organism abundances inthe laboratory and in natural, engineered and host environments.• Development of bioinformatic skills necessary to analyse and correlate the large-scaledatasets obtained from these approaches, and the statistical techniques needed to detect andquantify the significance of patterns within them.• Interaction with microbial ecologists, mathematical modellers, environmental scientists,wastewater treatment engineers and clinicians, allowing a system-level understanding of theecology of AMR gene persistence.• Potential later in the project to acquire modelling skills for the development of mathematicalmodels to predict changes in AMR gene abundance from process and community abundancedata.

Further Information:

Qualifications criteria Applicants applying for a MRC DTP in Precision Medicine studentship must have obtained, or be about to obtain, a first or upper second class UK honours degree or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology.

Residence criteria The MRC DTP in Precision Medicine grant provides funding for tuition fees and stipend for UK and EU nationals that meet all the required eligibility criteria.

Full qualifications and residence eligibility details are available here: http://www.mrc.ac.uk/skills-careers/studentships/studentship-guidance/student-eligibility-requirements/

https://www.ed.ac.uk/usher/precision-medicine/how-to-apply

References:

• Prestinaci, F. et al. (2015) Antimicrobial resistance: a global multifaceted phenomenon.Pathog. Glob. Health 109: 309-318.• Bouki, C. et al. (2013) Detection and fate of antibiotic resistant bacteriain wastewater treatment plants: a review. Ecotoxicol. Environ. Safety 91: 1-9.• Allen, H.K. et al. (2010) Call of the wild: antibiotic resistance genes in natural environments.Nature Rev. Microbiol. 8: 251-259.• Ofiteru, I.D. et al. (2010) Combined niche and neutral effects in a microbial wastewatertreatment community. Proc. Natl. Acad. Sci. USA 107: 15345-15350.

Subject Area(s):

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Role of Cold Shock Proteins in eliciting plant defence

Description:

Supervisors: Prof Maurice Gallagher   Dr NJ Holden

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

The last-line, broad-spectrum antimicrobials have now been withdrawn from use in horticulture. This leaves crop protection in a precarious position with inadequate means of controlling unwanted phytopathogens in crop production and food-spoilage. As such there is an urgent need for alternative approaches. Our previous AHDB-funded work has shown that elicitors that prime plant defences can be used to reduce bacterial disease on field vegetables. We have also identified chitosan as an elicitor and unravelled the molecular basis of immune priming in the protection against a fungal necrotroph.This proposal aims to expand on this work, to determine whether a family of ubiquitous bacterial proteins that are recognised by the plant in the basal immune response, can provide a feasible option for broad-spectrum control of bacterial pathogens. To address this question, we need to determine the functional role of the proteins, termed Cold Shock Proteins (CSP), in relation to bacterial colonisation of plants and the associated signalling pathways in plant defence. These aspects will be carried out with the aid of a model bacteria-plant system, using colonisation assays and whole transcriptomic analysis to characterise the plant defence response. The second stage will characterise the defence response elicited by a CSP peptide, to determine its value as a elicitor application.

Further InformationThe project is a joint collaboration between the University of Edinburgh (Edinburgh) and the James Hutton Institute (Dundee) and will involve research at both sites. The student will be registered for study at the UofE and will benefit from the well-established training programme within the School of Biological Sciences. In line with the collaboration the will also take part in relevant Hutton PG training processes.

 

Further Information:

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply  If you would like us to consider you for one of our scholarships you must apply by 12 noon on Monday 5th January 2018 at the latest.

 

References:

Craig, J. E., Boyle, D., Francis, K. P. & Gallagher, M. P. (1998). Expression of the cold-shock gene cspB in Salmonella typhimurium occurs below a threshold temperature. Microbiol-Uk 144, 697-704.

Holden, N., Jackson, R. W. & Schikora, A. (2015). Plants as alternative hosts for human and animal pathogens. Front Microbiol 6.

Wright, K. M., Chapman, S., McGeachy, K., Humphris, S., Campbell, E., Toth, I. K. & Holden, N. J. (2013). The endophytic lifestyle of Escherichia coli O157:H7: quantification and internal localization in roots. Phytopathol 103, 333-340.

 

Subject Area(s):

Microbiology Biotechnology Botany/Plant Science Molecular Biology Genetics Food Science/Nutrition Agricultural Sciences

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Stochastic modelling of cell movement and cell-cell interactions in cell populations

Description:

Supervisor: Dr Ramon Grima (Ramon.Grima@ed.ac.uk)    Prof Kevin Painter (Heriot Watt)

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

Cell movement and cell-cell interactions play key roles in determining correlations in the relative cell positions and velocities in cell populations. Mathematical models of such systems have typically been deterministic, i.e., consisting of a set of coupled partial differential equations describing the temporal and spatial evolution of the local cell number density. However it is well known that such models are only accurate in the limit of large population densities. It is often the case that the number density of cells is low in some regions of space; in such a scenario, random fluctuations in the cell numbers become important and cannot be neglected. Stochastic models hence constitute a more general framework for modelling cell populations but their analysis is substantially more difficult than that of deterministic models. In this project, the aim is to develop novel methods to extract biologically relevant information from stochastic models of cell populations, as well as to develop new computationally efficient means of simulating such models.

This project is ideal for a student with a Bachelors or Masters in Applied Mathematics, Physics or Engineering. Previous familiarity with mathematical modelling in biology is useful but not a necessity. The student will be given extensive training in deterministic and stochastic modelling in biology in their first year to ensure a solid foundation. The student will be part of the Grima group http://grimagroup.bio.ed.ac.uk/index.html, which is located in the Centre for Synthetic and Systems Biology (SynthSys) at the University of Edinburgh.

 

Further Information:

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-applyIf you would like us to consider you for one of our scholarships you must apply by 12 noon on the 5th January 2018 at the latest.

References:

Middleton A, Fleck C and Grima R. 2014. A continuum approximation to an off-lattice, individual-cell based model of cell migration and adhesion. Journal of Theoretical Biology 359: 220

Smith S, Cianci C and Grima R. 2016. Analytical approximations for spatial stochastic gene expression in single cells and tissues. J. R. Soc. Interface 13:20151051

 

Subject Area(s):

Cell Biology/Development, Biophysics, Theoretical Physics, Applied Mathematics

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*EPSRC* Developing realistic mathematical models of cell movement and interaction

Description:

Supervisors: Dr Ramon Grima (Ramon.Grima@ed.ac.uk) and Dr Nikola Popovic

Application deadline – 14 March 2018

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

Cell movement and cell-cell interactions play key roles in determining correlations in the relative cell positions and velocities in cell populations. Mathematical models of such systems have typically been deterministic, i.e., consisting of a set of coupled partial differential equations describing the temporal and spatial evolution of the local cell number density. However it is well known that such models are only accurate in the limit of large population densities. It is often the case that the number density of cells is low in some regions of space; in such a scenario, random fluctuations in the cell numbers become important and cannot be neglected. Stochastic models hence constitute a more general framework for modelling cell populations but their analysis is substantially more difficult than that of deterministic models. In this project, the aim is to develop novel methods to extract biologically relevant information from stochastic models of cell populations, as well as to develop new computationally efficient means of simulating such models.

This project is ideal for a student with a Bachelors or Masters in Applied Mathematics, Physics or Engineering. Previous familiarity with mathematical modelling in biology is useful but not a necessity.

The student will be given extensive interdisciplinary training in deterministic and stochastic modelling in biology in their first year to ensure a solid foundation. The student will be co-supervised by Dr. Ramon Grima  (http://grimagroup.bio.ed.ac.uk/index.html) and Dr. Nikola Popovic (http://www.maths.ed.ac.uk/school-of-mathematics/people?person=148) and will be part of the Centre for Synthetic and Systems Biology (SynthSys) at the University of Edinburgh.

 

Further Information:

This project is eligible for EPSRC funding and is open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) Deadline for applications: 14 March 2018

References:

Newman TJ, Grima R. 2004. Many-body theory of chemotactic interactions. Physical Review E. 70:051916.

Grima R. 2008. Multiscale modeling of biological pattern formation. Current Topics in Developmental Biology. 81:435.

Middleton A, Fleck C and Grima R. 2014. A continuum approximation to an off-lattice, individual-cell based model of cell migration and adhesion. Journal of Theoretical Biology 359: 220

Subject Area(s):

Mathematical Biology, Biophysics

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Exploring bacterial nanoparticle biosynthesis with synthetic biology

Description:

Supervisors: Dr Louise Horsfall (louise.horsfall@ed.ac.uk)

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

Morganella sp. has been shown to synthesise elemental metal nanoparticles [1] which can be used in applications such as antimicrobials [2] and catalysts [3]. Copper nanoparticle biosynthesis is a result of the bacterium’s heavy metal resistance pathway that transforms the copper ions into an inert form, minimising their interaction with the host cells. Establishing a library of characterised parts for gene expression will aid in making this strain a chassis for metal bioremediation applications.

In this PhD project the student will examine the native bacterial system, its potential for genetic manipulation and opportunities for its application. This may involve the characterisation of promoters and ribosomal binding sites with reporter genes, the optimisation of proteins in the synthesis pathway and investigation of the resultant effects on the metal resistance exhibited by the organism. The student will receive training in molecular biology and biochemistry, with an emphasis on synthetic biology approaches for characterising expression levels. The work in this project will provide the necessary tools and knowledge needed to improve upon the current nanoparticle synthesis yields for industrial purposes.

Lab website: http://horsfall.bio.ed.ac.uk/

 

Further Information:

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply If you would like us to consider you for one of our scholarships you must apply by 12 noon on Monday 5th January 2018 at the latest.

References:

[1] Ramanathan, R., M. R. Field, et al. (2013). "Aqueous phase synthesis of copper nanoparticles: a link between heavy metal resistance and nanoparticle synthesis ability in bacterial systems." Nanoscale 5(6): 2300-2306.

[2] Essa, A. M. M. and M. K. Khallaf (2016). "Antimicrobial potential of consolidation polymers loaded with biological copper nanoparticles." BMC Microbiology 16(1): 1-8.

[3] Sarkar, A., T. Mukherjee, et al. (2008). "PVP-Stabilized Copper Nanoparticles:  A Reusable Catalyst for “Click” Reaction between Terminal Alkynes and Azides in Nonaqueous Solvents." The Journal of Physical Chemistry C 112(9): 3334-3340.

Subject Area(s):

Synthetic Biology

Biotechnology

Biochemistry

Microbiology

Molecular Biology

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DNA repair mechanism and inhibition of Tdp1

Description:

Supervisors:  Dr Julia Richardson (julia.richardson@ed.ac.uk) and Dr Heidrun Interthal (heidrun.interthal@ed.ac.uk)

 

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

 

DNA topoisomerases have been described as “magicians of the DNA world”. They allow DNA strands and double helices to “pass through each other” thereby resolving topological strain created during DNA replication and transcription. To work their magic topoisomerases form a covalent complex with DNA. But if this complex is stalled, DNA damage ensues. This is the mode-of-action of the anti-cancer drug campothecin which intercalates at the topoisomerase IB (Topo IB)-DNA junction thereby stabilising the stalled nucleic acid-protein complex and ultimately leading to potentially lethal DNA double strand breaks.

 

However, the cell has a back-up plan: it can process stalled Topo IB-DNA complexes using the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1). Tdp1 hydrolyses the phosphodiester bond between a tyrosine side-chain on Topo IB and a DNA 3’ phosphate allowing the damaged DNA ends to be repaired. Blocking DNA repair by targeting human Tdp1 with small molecule inhibitors could be a useful adjunct to anti-cancer chemotherapy.

 

Our objectives are:(1)    To understand at the molecular level how human Tdp1 recognises, binds and processes its physiological Topo IB-DNA substrate. To address this we will use complementary structural and biochemical approaches.(2)    To identify small molecules that bind to and inhibit Tdp1. We will use both in silico and high-throughput in vitro approaches (beads coupled with chemical compounds). Potential inhibitors will be tested in vitro and in vivo in assays developed in the Interthal lab.The student will develop a broad range of skills in structural biology and biochemistry (in the Richardson lab) and in the molecular biology of DNA repair (in the Interthal lab). Skills developed will include protein expression and purification; protein-DNA cleavage, binding and foot printing assays; structure determination by X-ray crystallography; fluorescence spectroscopy and high-throughput screening.

More information about the lab, our interests and publications can be found here: http://richardson.bio.ed.ac.uk/

 

 

Further Information:

Effects of DNA and protein size on substrate cleavage by human tyrosyl-DNA phosphodiesterase 1. Interthal, H. & Champoux, J. J. (2011) Biochemical Journal. 436, 3, p. 559-66

Identification of a putative Tdp1 inhibitor (CD00509) by in vitro and cell-based assays.Dean RA, Fam HK, An J, Choi K, Shimizu Y, Jones SJ, Boerkoel CF, Interthal H, Pfeifer TA.J Biomol Screen. (2014) Dec;19(10):1372-82.

SCAN1 mutant Tdp1 accumulates the enzyme--DNA intermediate and causes camptothecin hypersensitivity. Interthal H, Chen HJ, Kehl-Fie TE, Zotzmann J, Leppard JB, Champoux JJ.EMBO J. 2005 Jun 15;24(12):2224-33.

References:

Effects of DNA and protein size on substrate cleavage by human tyrosyl-DNA phosphodiesterase 1. Interthal, H. & Champoux, J. J. (2011) Biochemical Journal. 436, 3, p. 559-66

Identification of a putative Tdp1 inhibitor (CD00509) by in vitro and cell-based assays.Dean RA, Fam HK, An J, Choi K, Shimizu Y, Jones SJ, Boerkoel CF, Interthal H, Pfeifer TA.J Biomol Screen. (2014) Dec;19(10):1372-82.

SCAN1 mutant Tdp1 accumulates the enzyme--DNA intermediate and causes camptothecin hypersensitivity. Interthal H, Chen HJ, Kehl-Fie TE, Zotzmann J, Leppard JB, Champoux JJ.EMBO J. 2005 Jun 15;24(12):2224-33.

Subject Area(s):

Structural biology, Biochemistry, Molecular Biology

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Developing Transposon Tools for DNA integration

Description:

Supervisor: Dr Julia Richardson (julia.richardson@ed.ac.uk)

 

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

 

Transposons make up a large proportion of most genomes and can move from one place to another, driving evolution and creating genome instability. Jumping genes have also given rise to new, useful cell functions e.g. V(D)J recombination and the adaptation process of CRISPR-Cas adaptive immunity. Eukaryotic DNA transposons (including Sleeping Beauty) are also useful tools for genomic manipulations. At the mechanistic level, DNA transposition is related to HIV-1 integration and V(D)J recombination.

 

To establish in molecular detail how DNA transposons move, we are characterising the structures of nucleoprotein complexes that form along the transposition pathway of the mariner/Tc1 transposon Mos1. In this way we have shown how the transposon is cut from host DNA1, and how the ends are held together2 and then inserted at a new genomic location. Most recently we have discovered a bend, flip and trap mechanism for transposon integration at TA sites3.

 

Our aim now is manipulate the transposase enzymes so that transposon integration can be (a) targeted to specific DNA sequences or (b) randomised. Our findings should be directly applicable to other mariner/Tc1 transposases, e.g. Sleeping Beauty, which is being used in human clinical trials to treat B-cell lymphoma by genetic engineering of T cells and in pre-clinical studies to reduce age-related macular degeneration. These findings have implications for our understanding of DNA rearrangements more broadly and will advance biotechnology applications of transposons.

 

The student will develop a broad range of skills in structural biology, biochemistry and molecular biology. Laboratory skills developed will include protein expression and purification; transposase-DNA cleavage, binding and integration assays; structure determination of transposase DNA complexes by X-ray crystallography; fluorescence spectroscopy.

 

More information about the lab, our interests and publications can be found here: http://richardson.bio.ed.ac.uk/

 

 

Further Information:

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply  If you would like us to consider you for one of our scholarships you must apply by 12 noon on Monday 5th January 2018 at the latest.

 

References:

1.    A bend, flip and trap mechanism for transposon integrationMorris, E., Grey, H., McKenzie, G., Jones, A. & Richardson, J. (2016) eLIFE. e15537

2.    Structural role of the flanking DNA in mariner transposon excisionDornan, J., Grey, H. & Richardson, J. M. (2015) Nucleic Acids Research. 43(4) 2424-2432

3.    Molecular Architecture of the Mos1 Paired-End Complex: The Structural Basis of DNA Transposition in a EukaryoteRichardson, J. M., Colloms, S. D., Finnegan, D. J. & Walkinshaw, M. D. (2009) Cell. 138, (6), 1096-1108

Subject Area(s):

Biochemistry, Structural Biology, Biophysics

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Cell engineering strategies to enhance production of next-generation biologics

Description:

Supervisors:  Prof Susan Rosser (Susan.Rosser@ed.ac.uk), Dr Hannah Florance (Hannah.Florance@ed.ac.uk) and Dr Neha Dhami (UCB)

 

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

 

The Chinese Hamster Ovary (CHO) cell is the most widely used industrial expression system, generating ~70% of biopharmaceuticals (including multiple monoclonal antibodies) with a market value >$100 billion. However, many ‘difficult-to-express’ biologics – including novel molecules such as bi- and tri-specific antibodies – give unpredictably lower titres and additional complexities, requiring extensive cell line and process development. Productivity can be compromised by transgene suppression and bottlenecks in translation, trafficking, processing or secretion. The aim of this project is to use a combination of synthetic biology, genetic engineering tools, and modern ‘omics platforms (genomics, metabolomics and proteomics) to discover and address bottlenecks in the production of novel biologics in CHO cells.

The student will learn cutting edge gene editing tools (including CRISPR/Cas9), synthetic biology tools and metabolomics and proteomics platforms.

 

The project will be supervised jointly by Prof. Susan Rosser, Dr Hannah Florance and Dr Neha Dhami (UCB). Prof Rosser is professor of synthetic biology, director of the UK Centre for Mammalian Synthetic Biology (the ‘Centre’, http://www.synbio.ed.ac.uk) and co-director of the Edinburgh Genome Foundry (http://www.genomefoundry.org). Dr Hannah Florance leads the metabolomics research at the Centre. Dr Neha Dhami is a research scientist in the Protein Sciences group at UCB.

 

The PhD student will become part of a cohort of students linked to the research of the new UK Centre for Mammalian Synthetic Biology based at the University of Edinburgh. Through support from the Research Council’s Synthetic Biology for Growth programme and of the BBSRC, EPSRC and MRC, the University has been awarded ~ £18M in funding to establish a national facility for DNA synthesis (the Edinburgh Genome Foundry) and one of six UK Centres of Excellence in synthetic biology. More information about our Centre can be found at http://www.synbio.ed.ac.uk and follow us on Twitter @SynthSysEd.

 

This is an exciting opportunity to be at the cutting edge of this fast moving area of science and technology in world-leading research institute and in collaboration with an innovative multinational. We are looking for highly motivated graduates who are enthusiastic about the potential of this new area of science and keen to work across disciplines.

 

This project is funded through an EPSRC CASE Award in collaboration with the company UCB. It therefore provides an excellent opportunity to work closely with industry professionals including working for at least three months on site at the company in Slough.

Further Information:

Please follow the instructions on how to apply: http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

 

This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body. The successful candidate must be able to start by 1st April 2018 or earlier. We will accept applications until a suitable candidate is appointed.

References:

Subject Area(s):

Synthetic biology, CHO cell engineering, metabolomics, proteomics

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The role of memory in cellular decision-making and fitness

Description:

Supervisor: Prof Peter Swain

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

changes. Do cells remember and use their memory to alter their behaviour? Are current events used to predict and prepare for future events? Are memories passed on to new daughter cells or kept by the mother?Using single-cell microscopy and microfluidic technology, you will investigate cellular responses and memory in budding yeast. We have developed a microfluidic device, called ALCATRAS, which uses micron-sized "jails" to trap an initial population of cells. All daughter cells of the trapped cells are eventually washed away by the flow of media through the device, and we can therefore typically monitor individual cells for around 20 divisions, and often to senescence. By changing pressure on the two inflow channels, we can alter the extracellular media every few seconds and move cells, for example, in to and out of stress.

You will study the response of single cells to repetitive occurrence of stress such as exposure to extracellular media that is low in nutrients. Using fluorescent proteins, you will follow new gene expression and the intracellular movement of transcription factors. You will measure cell fitness using software that automatically counts the number of divisions each cell undergoes from the microscopy images. By correlating the cellular response with fitness, you will be able to classify cellular responses as successful or unsuccessful. Mutations and mathematical modeling will be used to explore mechanisms.The aim is to understand the advantages and biochemistry of memory. Initially, you will study changes in carbon sources and later changes in nitrogen sources, an under explored area despite control by the well-known TOR kinase.

swainlab.bio.ed.ac.uk

 

Further Information:

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply If you would like us to consider you for one of our scholarships you must apply by 12 noon on Monday 5th January 2018 at the latest. 

References:

Mitchell A, Lim W. Cellular perception and misperception: Internal models for decision-making shaped by evolutionary experience. Bioessays. 2016; 38: 845-9

Stockwell SR, Landry CR, Rifkin SA. The yeast galactose network as a quantitative model for cellular memory. Mol Biosyst. 2015; 11: 28-37

Crane MM, Clark IB, Bakker E, Smith S, Swain PS. A microfluidic system for studying ageing and dynamic single-cell responses in budding yeast. PLoS One. 2014;9:e100042

 

Subject Area(s):

Biophysics

Microbiology

Molecular Biology

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A whole-cell model to predict changes in translation and growth during cellular stress

Description:

Supervisor: Prof Peter Swain

This position will close when a suitable candidate is appointed.

Interested individuals please contact Professor Swain direct: peter.swain@ed.ac.uk

Expressing synthetic circuits imposes a burden on the cell and being able to predict the effects of this burden will improve the efficiency and so the potential of synthetic biology. We will determine how exogenous gene expression changes the growth rate, levels of tRNAs, and transcription in general in budding yeast. These results will be included in a whole-cell model through more realistic models of gene expression with the aim to predict changes in growth rate as levels of extracellular nutrients are altered. Using fluorescently tagged proteins and a microfluidic system, an additional focus will be on identifying transcription factors that are potential set points and that respond both to the stress imposed by a synthetic circuit and the dynamics of that stress (for example, rapid versus slow induction).

The PhD is generously funded through the SynCrop Marie Sklodowska-Curie Innovative Training Network and is open to all EU students.

We expect particularly close collaboration with our partners at the University of Hamburg, Insilico Biotechnology in Germany, and the Free University of Amsterdam, as well as with others within SynCrop.

http://www.syncrop.org/http://swainlab.bio.ed.ac.uk

 

Further Information:

This position will close when a suitable candidate is appointed.

The PhD is generously funded through the SynCrop Marie Sklodowska-Curie Innovative Training Network and is open to all EU students.

Interested individuals please contact Professor Swain direct: peter.swain@ed.ac.uk

References:

Granados AA, Crane MM, Montano-Gutierrez LF, Tanaka RJ, Voliotis M, Swain PS.  Distributing tasks via multiple input pathways increases cellular survival in stress. Elife. 2017;6: e21415

Weiße AY, Oyarzún DA, Danos V, Swain PS. Mechanistic links between cellular trade-offs, gene expression, and growth. Proc Natl Acad Sci U S A. 2015;112:E1038-47

 

Subject Area(s):

Molecular biology; biophysics; biotechnology; bioinformatics

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A whole-cell model to predict the energetic costs imposed by synthetic constructs

Description:

Supervisor: Prof Peter Swain

This position will close when a suitable candidate is appointed.

Interested individuals please contact Professor Swain direct: peter.swain@ed.ac.uk

Expressing synthetic circuits imposes a burden on the cell and being able to predict the effects of this burden will improve the efficiency and so the potential of synthetic biology. Using fluorescent reporters, we will first determine how mitochondrial potential, ATP, and intracellular pH change with growth rate in budding yeast and then combine these biophysical measurements with a model of volume regulation into a whole-cell model. The aim is to predict biochemical "set-points" that can be controlled to reduce the effects of synthetic constructs on cellular physiology.

The PhD is generously funded through the SynCrop Marie Sklodowska-Curie Innovative Training Network and is open to all EU students.

We expect particularly close collaboration with our partners at the University of Groningen, the DSM Biotechnology Centre in the Netherlands, and the Free University of Amsterdam, as well as with others within SynCrop.

Further Information:

This position will close when a suitable candidate is appointed.

The PhD is generously funded through the SynCrop Marie Sklodowska-Curie Innovative Training Network and is open to all EU students.

Interested individuals please contact Professor Swain direct: peter.swain@ed.ac.uk

References:

Weiße AY, Oyarzún DA, Danos V, Swain PS. Mechanistic links between cellular trade-offs, gene expression, and growth. Proc Natl Acad Sci U S A. 2015;112:E1038-47

Molenaar D, van Berlo R, de Ridder D, Teusink B. Shifts in growth strategies reflect tradeoffs in cellular economics. Mol Syst Biol. 2009; 5: 323

 

Subject Area(s):

Molecular biology; biophysics; biotechnology; bioinformatics

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*EPSRC* A Synthetic Biology Approach Towards the Bio-production of Medicinally-relevant Natural Products

Description:

Supervisors: Dr Stephen Wallace (Stephen.Wallace@ed.ac.uk) and Prof Susan Rosser (Susan.Rosser@ed.ac.uk)

Application deadline – 14 March 2018

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

Using synthetic biology to produce natural products of medicinal importance has revolutionised the field of biotechnology. By assembling the genetic components of a given synthetic pathway in a host microorganism it is now possible to overproduce these complex molecular structures directly from renewable feedstocks via fermentation. However, in the absence of any genetic information from the native producer or an elucidated biosynthetic pathway, heterologous transfer or de novo synthesis of the requisite genetic “parts” for this approach becomes limiting. This is particularly problematic when one considers natural products from plants, many of which are used in modern-day medicine. For this reason, these compounds are still manufactured via extraction from the native plant, or via chemical synthesis using non-renewable fossil fuels. This project will develop a new approach towards a family of plant-derived natural products in the organisms E. coli and S. cerevisiae using a combination of biosynthetic logic, metabolic engineering and synthetic biology.

This will be a multi-disciplinary project based at the Institute for Bioengineering (School of Engineering), the Institute for Quantitative Biology, Biochemistry and Biotechnology (School of Biological Sciences), and the Centre for Synthetic and Systems Biology – all located at the University of Edinburgh. The successful candidate will be exposed to a variety of modern laboratory techniques, including transcriptome-guided enzyme discovery, proteomics/metabolomics, recombinant DNA assembly and CRISPR-mediated genome editing. The successful candidate should have prior experience in molecular biology and basic microbiology, alongside an enthusiasm to learn more about this emerging field of research.

Lab Websites:

Wallace Lab: http://wallacelab.bio.ed.ac.uk

Dr Solis: https://www.eng.ed.ac.uk/about/people/dr-leonardo-rios-solis

Rosser Lab: http://rosser.bio.ed.ac.uk

Further Information:

This project is eligible for EPSRC funding and is open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) Deadline for applications: 14 March 2018

References:

Subject Area(s):

Biotechnology, Natural Products, Synthetic Biology, Molecular Biology, Microbiology

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Synthetic biology-enabled new generation biosensors for global health and environment challenges

Description:

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

The traditional laboratory-based analytical assays for bacterial pathogens and environmental toxins are expensive, time consuming and normally require specialised personnel and complex equipment. This restricts their use in resource limited areas and developing countries where lack sufficient skilled personnel and healthcare facilities to rapidly identify the risks. There is therefore an urgent need to provide simple cost effective, fast on-site sensing solutions for pathogens (e.g. diarrhea related Shigella flexneri) and toxins (e.g. arsenic or pesticides in contaminated drinking water) associated with fatal bacterial infections and contaminated water or land resources.  

This project aims to use innovative synthetic biology approaches to develop new generation biosensors to address these daunting global health and environmental challenges. In particular, we will develop robust, fast, inexpensive and portable cell-free/paper-based biosensors that are readily deployable in the field with minimal human intervention and/or resources. The project is based on our prior ample experience and expertise in engineering synthetic cell-based biosensors for environmental toxins and pathogens with programmable sensitivity and selectivity. Advanced signal processing and amplifying gene networks may be used within these sensor circuits to boost the sensor sensitivity to meet their real world detection requirement. Novel encapsulation and packaging methods will also be developed to significantly increase the robustness, stability and shelf life of the resulting sensors. The technology and approaches developed will find diverse applications in environmental, biotechnological and medical settings.  

The project will provide you a comprehensive training of advanced molecular and genetic tools, innovative microbiology and bioelectronics techniques and computational skills. This project will be supervised by Dr Baojun Wang at the Centre of Synthetic and Systems Biology giving the student an interdisciplinary research experience in the fields of synthetic biology and global health. The student will also have the opportunity to work with and spend an internship with the project industrial partners.

 

Further information about the lab can be found at http://wang.bio.ed.ac.uk/ and informal enquiries may be made to baojun.wang@ed.ac.uk.

Further Information:

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply  If you would like us to consider you for one of our scholarships you must apply by 12 noon on Monday 5th January 2018 at the latest.

 

References:

1. Slomovic et al. (2015) “Synthetic biology devices for in vitro and in vivo diagnostics”, PNAS, 112:14429–14435

2. Wang et al. (2013) “A modular cell-based biosensor using engineered genetic logic circuits to detect and integrate multiple environmental signals”, Biosensors & Bioelectronics, 40:368-376.

3. Wang et al, “Engineering modular and tunable genetic amplifiers for scaling transcriptional signals in cascaded gene networks”, Nucleic Acids Research, 2014, 42:9484-92

 

Subject Area(s):

Synthetic biology, Biotechnology, Bioengineering, Microbiology, Molecular Biology, Global health

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Programmable precision guided bacteriophages for selective killing of AMR gut pathogens

Description:

Supervisor:  Dr Baojun Wang (baojun.wang@ed.ac.uk)

 

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

 

Infectious diarrhea is a major cause of infant mortality and adult morbidity in developing countries with estimated 1 to 2 million deaths per year. The global burden of food-borne diseases is still increasing despite major public health efforts due to poor sanitation and emergence of new strains of antimicrobial resistant (AMR) enteropathogens. While antibiotics and specific naturally isolated bacteriophages may be applied for the cure, they generally lack the specificity and programmability to predictably control the population of many other commensal species in the gut microbiome. In addition, due to increasing AMR to existing antibiotics and natural phages current therapies are at danger to become quickly ineffective and outdated. Here we will engineer bacteriophages to selectively target gut pathogens such as E. coli and Salmonella that cause widespread environmental enteropathy in infants in developing countries. We will program the CRISPR-Cas9 (clustered, regularly interspaced short palindromic repeats–CRISPR-associated proteins) nucleases to cut the chromosomes of the target pathogens, and test their ability to block infection in a mouse gut colonization model while leaving the non-pathogenic and often beneficial bacteria largely intact.

The project will provide the student a comprehensive training of advanced molecular genetic tools, innovative synthetic biology technologies, pathological basis of infectious diseases and computational bioinformatics skills. The research will gives the student sufficient training and experience to work in a multi-disciplinary research environment and team, equipped with the ability to initiate and perform innovative frontier research in synthetic biology with application in biomedicine and to prepare well for his/her future research career. The student may also benefit from the opportunity to work collaboratively with some of our healthcare and industrial partners in biomedicine.  

Further information about the lab can be found at http://wang.bio.ed.ac.uk/ and informal enquiries may be made to baojun.wang@ed.ac.uk.

Further Information:

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply  If you would like us to consider you for one of our scholarships you must apply by 12 noon on Monday 5th January 2018 at the latest.

 

References:

Newell et al., Food-borne diseases - the challenges of 20 years ago still persist while new ones continue to emerge, Int J Food Microbiol, 2010, 139, S3-15

Bikard et al., Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials, Nature Biotechnology, 2014, 32:1146-1150

Brown R, Lengeling A and Wang B, “Phage engineering: how advances in molecular biology and synthetic biology are being utilized to enhance the therapeutic potential of bacteriophages”, Quantitative Biology, 2017, 5(1):42-54

Subject Area(s):

Synthetic biology, Biotechnology, Bioengineering, Microbiology, Molecular Biology, Infectious disease

 

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Genetic programs for advanced cellular information processing and behaviour control

Description:

Supervisor:  Dr Baojun Wang (baojun.wang@ed.ac.uk)

 

Interested individuals must follow Steps 1, 2 and 3 at this link on how to applyhttp://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

 

Bacterial cells live in an ever changing environment and therefore are equipped with specific genetically-encoded sensors and signalling networks to continuously perceive and process the various environmental signals. In this sense, cells can be viewed as replicating living computers but with biochemical inputs and outputs. This project aims to design and construct synthetic gene circuits to program live bacterial cells with designer functions, in particular for advanced sensing, computing, information processing and control of multiple cellular and environmental signals with application, for example, in microbial cell factories.

You will be guided to construct various genetic programs including novel sensors, genetic logic gates, amplifiers, computing and memory circuits. The layering and integration of these circuit modules will lead to a programmable biological computer. The biological computer will then enable the programmed cells to have a range of intelligent capabilities for application in areas including biosensing, biomanufacturing and biotherapies. By example, the engineered tools can be applied to significantly enhance the production yields of some difficult-to-express, large or toxic therapeutic proteins in industrial scale bioreactors. You will be guided to develop new biological circuit design principles by exploiting design principles in other engineering systems such as modularity, orthogonality, systematic characterization and modelling to increase the predictability and scalability of gene circuit design and assembly.The project will provide the student a comprehensive training of advanced molecular cloning and genetic tools, innovative microbiology and synthetic biology techniques and computational modelling skills. The research thus gives the student an inter-disciplinary research experience and cutting edge technologies exposure to prepare well for his/her future research career. The student may also benefit from the opportunity to work collaboratively with some of our industrial partners in biotechnology.

 

Further information about the lab can be found at http://wang.bio.ed.ac.uk/ and informal enquiries may be made to baojun.wang@ed.ac.uk.

 

Further Information:

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply  If you would like us to consider you for one of our scholarships you must apply by 12 noon on Monday 5th January 2018 at the latest.

 

References:

Wang, Kitney, Joly and Buck, “Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology”, Nature Communications, 2011,2:508  (Reported by Financial Times, EPSRC, European Commission, Electronics Weekly, Science Daily and Imperial College among others)

Wang, Barahona and Buck, “A modular cell-based biosensor using engineered genetic logic circuits to detect and integrate multiple environmental signals”, Biosensors and Bioelectronics, 2013, 40, 368-376  

Bradley and Wang, “Designer cell signal processing circuits for biotechnology”, New Biotechnology, 2015, 32:635-643

Subject Area(s):

Synthetic biology, Biotechnology, Bioengineering, Biocomputing, Microbiology, Molecular Biology

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*EPSRC* Synthetic biology-enabled new generation biosensors for global health and environment challenges

Description:

Supervisor:  Dr Baojun Wang (Baojun.Wang@ed.ac.uk)

Application deadline – 14 March 2018

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

The traditional laboratory-based analytical assays for bacterial pathogens and environmental toxins are expensive, time consuming and normally require specialised personnel and complex equipment. This restricts their use in resource limited areas and developing countries where lack sufficient skilled personnel and healthcare facilities to rapidly identify the risks. There is therefore an urgent need to provide simple cost-effective, fast on-site sensing solutions for pathogens (e.g. diarrhea-related Shigella flexneri), toxins (e.g. arsenic or pesticides) and metabolites (e.g. phenylalanine in phenylketonuria) associated with fatal infectious/metabolic diseases and contaminated water or land resources.       This project aims to use innovative synthetic biology approaches to develop new generation biosensors to address these daunting global health and environmental challenges. In particular, we will develop robust, fast, inexpensive and portable cell-free/paper-based biosensors that are readily deployable in the fieled with minimal human intervention and/or resources. The project is based on our prior ample experience and expertise in engineering synthetic cell-based biosensors for environmental toxins and pathogens with programmable sensitivity and selectivity. Advanced signal processing and amplifying gene networks may be used within these sensor circuits to substantially boost sensor sensitivity to fulfil their real world detection requirement. Novel encapsulation and packaging methods will also be developed to significantly increase the robustness, stability and shelf life of the resulting sensors. The technology developed will find diverse applications in environmental, biotechnological and medical settings.       The project will provide you a comprehensive training of advanced molecular and genetic tools, innovative microbiology and bioelectronics techniques and computational skills. This project will be supervised by Dr Baojun Wang, a group leader in the world-leading Centre of Synthetic and Systems Biology of the University of Edinburgh, giving the student an interdisciplinary research experience in the fields of synthetic biology and global health as well as the opportunity of working with relevant project industrial partners.

 

 

 

Further Information:

This project is eligible for EPSRC funding and is open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) Deadline for applications: 14 March 2018 Further information about the lab can be found at http://wang.bio.ed.ac.uk/ and informal enquiries may be made to baojun.wang@ed.ac.uk.

References:

1. Slomovic et al. (2015) “Synthetic biology devices for in vitro and in vivo diagnostics”, PNAS, 112:14429–14435

2. Wang et al. (2013) “A modular cell-based biosensor using engineered genetic logic circuits to detect and integrate multiple environmental signals”, Biosensors & Bioelectronics, 40:368-376.

3. Wang et al, “Engineering modular and tunable genetic amplifiers for scaling transcriptional signals in cascaded gene networks”, Nucleic Acids Research, 2014, 42:9484-92

 

Subject Area(s):

Synthetic biology, Biomedical engineering, Biotechnology, Microbiology, Molecular Biology, Biochemistry, Public Health & Epidemiology

 

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