2019 Available Projects
Below are a list of PhD Projects available at Imperial College and Royal Holloway for October 2019 entry. Please contact the relevant supervisor(s) for any questions.
2019 Available Projects
Gilestro and Windblicher: "Phenoscopes: high-throughput Platform for Phenotypical Typing of Insect Strains"
Project Title: Phenoscopes: A high-throughput Platform for Phenotypical Typing of Insect Strains for the “Insects as Source of Proteins” Industry
Project Description: Creating sustainable, carbon neutral, protein-rich food sources is one of the leading priorities of this century, worldwide. The aim of this project is to create a repertoire of genetically selected and/or engineered insects, possibly aimed at mass scale production for the food industry for animal and, eventually human, consumption. The project will be carried in collaboration with N. Windblicher (expert in genetic manipulation of non-model-organism species) and BetaBugs, a small but promising UK startup. The project will consist of three work packages:
- WP1: Evolve a device we recently developed for sleep analysis in Drosophila (the ethoscope, Geissmann et al. PLoS Biology 2017) into a device that can be used for large scale phenotypical analysis of Hermetia illucens (Black Soldier flies), the most commonly used insect species in the food industry. Ethoscopes employ video-based machine-learning technology to detect activity and behaviour in fruitflies and phenoscopes, our proposed evolution, will also be able to detect metabolic features such as growth rate, body size, preferential temperature and humidity conditions of growth.
- WP2: Establish H. illucens as genetically amenable organism, using CRISPR-based homologous recombination techniques.
- WP3: Study the metabolism and behaviour of H. illucens
More information on http://lab.gilest.ro
Murray and Rutherford: "Structural Basis of Nitrogenase Assembly and Oxygen Protection"
Project Title: Structural Basis of Nitrogenase Assembly and Oxygen Protection
Project Description: Biological nitrogen fixation is catalysed by nitrogenase. Nitrogenase is a complex enzyme, with three subunits, binding several cofactors. The best studied nitrogenase has molybdenum in the active site, and is encoded by nif genes. The nif operon encodes other assembly factors and conserved proteins of unknown function. Two alternative nitrogenases, with vanadium or iron instead of molybdenum, encoded by vnf and anf clusters, are even less well-characterised. Nitrogenase is inactivated by oxygen, and this vulnerability, combined with the complicated assembly, makes heterologous expression of nitrogenase challenging. However, expression of nitrogenase in crop plants could revolutionise agriculture, by ending the need for polluting nitrogenous fertilizers.
We have recently biochemically and structurally characterised the Anf3 protein, which protects the iron-only nitrogenase from oxygen. Anf3 is associated with two other conserved genes anf12, which are of unknown function but also essential for iron-only nitrogenase. Our work on the oxygen-protective FeSII protein (PDB 5FRT), is a prerequisite to determining the mechanism of nitrogenase protection. In this project we will structurally and functionally characterise the remaining nif and alternative nitrogenase genes. This will require biochemistry and X-ray crystallography in the Murray group, and biophysical techniques such as EPR and spectroelectrochemistry for the bioinorganic chemistry in the Rutherford group.
Kuimova and Vilar: "Imaging G-quadruplex DNA in Telomeres of Live Cells Using FLIM"
Project Title: Imaging G-quadruplex DNA in Telomeres of Live Cells Using FLIM
Project Description: This project will focus on the development of novel probes and imaging techniques to monitor the formation of non-canonical DNA structures termed G-quadruplexes. Over the past few years, mounting experimental evidence suggested that these non-canonical DNA structures play essential biological roles. However, to date there is still little direct evidence that G-quadruplexes are functional in live cells. This work will build on our ‘proof of concept’ study using Fluorescence Lifetime Imaging Microscopy (FLIM) that has been published in [A. Shivalingam, et al, Nature Commun., 2015, 6, 8178].
The successful applicant will perform cellular imaging including FLIM and spectroscopic characterisation of new fluorescent probes and their interaction with various DNA topologies. The main focus will be to use these techniques to study G-quadruplex formation and its relationship to cell function. There is also scope to design and synthesise optical probes, provided the applicant has the right expertise and an aptitude for synthesis.
Isalan and Brickley: "Zinc Finger-based Gene Therapy in Huntington’s Disease"
Project Title: Zinc Finger-based Gene Therapy in Huntington’s Disease
Project Description: Biopharmaceuticals, new medical drugs produced using industrial biotechnology processes, are one of the fastest growing sectors of the pharmaceutical industry. Many important biopharmaceuticals, such as therapeutic antibodies with commercial sales in the billions of pounds are glycoproteins. The type of sugar molecule on the biopharmaceuticals can greatly affect their functional properties. This can greatly affect the potential therapeutic value of the products.
The project will fundamentally involve the development and application of new bioprocesses to improve the production of consistent, high-quality glycoprotein therapeutics. This will include glycoengineering of CHO cells, altering the expression of glycosyltransferases, glycosidases and other key biosynthetic enzymes and transporters to both control and homogenize glycosylation patterns. Also, the development of a cell free artificial Golgi with a defined and tunable glycosylation machinery to reduce glycosylation variability. The impact of these approaches on glycoprotein glycosylation will be defined by mass spectrometric analysis, the data from which will be fed back to facilitate integrative design improvements.