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 Elise Cachat *EASTBIO* Developing genome-editing techniques to investigate biomineralisation in coccolithophores
Prof Susan Rosser Cell engineering strategies to enhance production of next-generation biologics
Dr Stephen Wallace *EASTBIO* Chemo-enzymatic Methods for the in situ Detection and Modification of Metabolites from Engineered Metabolic Pathways (CASE)

Project Details

*EASTBIO* Developing genome-editing techniques to investigate biomineralisation in coccolithophores

Description:

Supervisors:  Dr Fabio Nudelman (fabio.nudelman@ed.ac.uk), Dr Elise Cachat (Elise.Cachat@ed.ac.uk) and Dr Dominic Campopiano (dominic.campopiano@ed.ac.uk

 

Biomineralisation is the dynamic process whereby an organism employs a range of specialized proteins, lipids and polysaccharides to control mineral precipitation and produce a functional mineralised structure. Coccolithophores are unicellular marine algae that produce coccoliths – disk-shaped assemblies of calcium carbonate crystals in the form of calcite – that play an important role in the global carbon cycle, allowing the excess greenhouse CO2 to be removed from Earth atmosphere through photosynthesis and calcification. The formation of the calcite disks is a fascinating process that is carried out within mineralisation vesicles inside the cells, where polysaccharides are thought to control the nucleation, growth and morphology of the crystals (Sviben et al., 2016). Once the mineralisation is complete, the vesicle is transported to the cell membrane and the mature mineral is extruded. While the roles of the polysaccharides in controlling crystal nucleation and growth have been investigated over several years, the biochemical pathways that control mineralisation are still unknown. In particular, genetic models that will enable a detailed in vivo study of the specific role of particular proteins and signalling pathways to biomineralisation are lacking in coccolithophores.

 

Two recent developments have opened up a largely unexplored route of genetic manipulation in these microorganisms: (i) a new method for DNA nuclear transfer in Pleurochrysis carterae, a member of the coccolithophore family (Endo et al., 2016); and (ii) the genome of the dominant coccolithophore Emiliania huxleyi was sequenced (Read et al., 2013). This project aims at building upon these recent advances to:

1. develop efficient methods of genome-editing in these coccolithophorid algae;

2. engineer fluorescently-tagged reporter models for key components of the mineralisation vesicle (e.g. actin, tubulin);

3. monitor by real time fluorescent microscopy the transport and extrusion of mineralisation vesicles in different species;

4. investigate the role of sphingolipid biosynthesis and trafficking in this transport.

 

The supervisory team of this project merges expertise in chemistry/biomineralisation (FN, http://www.chem.ed.ac.uk/staff/academic-staff/dr-fabio-nudelman), sphingolipid metabolism (DC, http://www.campopianosite.wixsite.com/campopiano) and molecular genetics (EC, http://www.ed.ac.uk/biology/people/profile/ecachat), which, in addition to training in scientific research and analytical methods, will ensure the acquisition of skills in several areas, including electron microscopy and crystallography, cell culture, cellular and molecular biology techniques and fluorescence/confocal microscopy.

Further Information:

Project and application details can be found at the website below. You must follow the instructions on the EASTBIO website for your application to be considered.

THIS PROJECT IS HOSTED BY THE SCHOOL OF CHEMISTRY

Deadline for applications: 22 May 2017This 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.http://www.eastscotbiodtp.ac.uk/how-apply-0 (and submit your application via the link for the School of Chemistry)

References:

Sviben, S. et al. A vacule-like compartment concentrates a disordered calcium phase in a key coccolithophorid alga. Nature Comm. 7, 11228 (2016).

Endo, H. et al. Stable Nuclear Transformation System for the Coccolithophorid Alga Pleurochrysis carterae. Sci. Rep. 6, 22252 (2016).

Read, B.A. et al. Pan genome of the phytoplankton Emiliania underpins its global distribution. Nature 499: 209-13 (2013).

Subject Area(s):

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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.Closing date for applications:  Friday 14 July 2017

References:

Subject Area(s):

Synthetic biology, CHO cell engineering, metabolomics, proteomics

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*EASTBIO* Chemo-enzymatic Methods for the in situ Detection and Modification of Metabolites from Engineered Metabolic Pathways (CASE)

Description:

Supervisors: Dr Stephen Wallace (stephen.wallace@ed.ac.uk) and Professor Susan Rosser (susan.rosser@ed.ac.uk)

 

Industrial biotechnology continues to be driven by advances in the field of synthetic biology. New designer synthetic pathways can now be readily assembled within a variety of host microorganisms, allowing direct access to an ever-expanding range of important small molecules from renewable materials via fermentation. Multiple products can also be accessed from a single metabolic pathway by altering the specificity of biosynthetic enzymes via directed evolution. This involves the generation of large libraries of mutants from which the most active variants are selected. For small molecule producing microorganisms this frequently involves extracting the target metabolite(s) and quantifying their production levels using analytical methods such as HPLC and/or LC-/GC-MS. This process is time-consuming, inefficient, expensive and represents a significant bottleneck in the development of new industrial bioprocesses. Chemo-enzymatic methods for the in situ detection and quantification of metabolite levels during screening studies remains an underexplored area of synthetic biotechnology. The development of such methodology would greatly expedite the overall strain engineering process, reduce cost, and have widespread impact across the industrial biotechnology sector.

This project aims to address this problem by developing novel reactions capable of intercepting metabolites in situ and converting them into coloured and/or fluorescent products. This will allow the rapid identification of optimal pathway variants in simple culture and/or plate-based phenotypic screens, without the need for further extraction and analysis. This will involve the use of both enzymatic and non-enzymatic chemistries, which will be designed to occur either within the surrounding growth medium or at the cell membrane. Ultimately, this approach will be applied to a range of target small molecule metabolites and pathways of interest to both academia and industry.

The highly multi-disciplinary nature of this project will enable students to gain a strong proficiency in synthetic biology, cellular engineering, organic synthesis and industrial bioprocess development.

 

This project will likely be best suited to students from a biotechnology/biochemistry/organic synthesis background with an interest in synthetic biology, synthetic organic chemistry and/or industrial biotechnology.

 

This project will also involve a 3-month industrial placement at Ingenza.

 

Further Information:

This project will be co-supervised by Dr Stephen Wallace and Professor Susan Rosser at the Institute of Quantitative Biology, Biochemistry and Biotechnology (IQB3) in the School of Biological Sciences at the University of Edinburgh, and our industrial partner Ingenza. This research will expose students to a variety of techniques including recombinant DNA assembly (Rosser/Ingenza), genome engineering (Rosser/Ingenza), enzyme overproduction and purification (Rosser/Wallace/Ingenza), unnatural amino acid incorporation (Wallace), biocompatible catalyst design (Wallace) and analysis via HPLC, GC/LC-MS, NMR spectroscopy and mass spectrometry (Wallace/Ingenza).

 

Project and application details can be found at the website below. You must follow the instructions on the EASTBIO website for your application to be considered.

Deadline for applications: 5 June 2017This 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.http://www.eastscotbiodtp.ac.uk/how-apply-0

References:

[1]  S. Wallace, E. P. Balskus, Curr. Opin. Biotechnol. 2014, 30, 1–8

[2]  S. Wallace, E. P. Balskus, Angew. Chem. Int. Ed. 2015, 54, 7106–7109

[3]  S. Wallace, E. P. Balskus, Angew. Chem. Int. Ed. 2016, 55, 6023–6027

Subject Area(s):

Industrial biotechnology & bioenergy

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