We are looking for a candidate to take up an EPSRC-funded DTP PhD Studentship co-supervised by Prof. Mark Isalan (http://www.imperial.ac.uk/people/m.isalan) and Dr. Robert Endres (http://www.imperial.ac.uk/people/r.endres). The project will develop computational approaches to guide engineering of synthetic biology gene circuits for spatial pattering.

Project details:

The self-organisation of spatial patterns and structures in developmental biology is a fundamental problem that promises to underpin our future efforts in tissue engineering and regenerative medicine. Computational Systems Biologists and Synthetic Biologists can together provide a bridge from theory towards practical applications, by building working prototype systems. In our groups, we have already built simple synthetic patterns using cells, and are working towards our dream of engineering self-organising tissues and organs at will. Although several patterning mechanisms have been proposed in classical developmental biology, the Turing pattern mechanism is unique in terms of self-correction, and economy of design, and regular patterns have never been constructed ab initio using defined biological components. It is therefore a tantalising engineering and modelling target, and we have chosen to engineer these systems in bacterial 'lawns' or biofilms. In this theory project in the Endres group, we will implement a biophysical reaction-advection diffusion model for such a growing biofilm, considering gene expression, as well as fluid- and cell-mechanical aspects. Theoretical predictions will be tested in the nearby Isalan lab.

How to apply:

Please email Mark Isalan (m.isalan@imperial.ac.uk) and Robert Endres (r.endres@imperial.ac.uk) and include in your application:

• A cover letter
• Your CV
• Your transcript
• Three references sent directly from the referees

 Qualifications/ Eligibility

Candidates must have (or expected to have by October 2019) at least a 2.1 BSc, or equivalent qualifications.

All students will participate in the MRes in Systems and Synthetic Biology (at Imperial College London), starting 1 October 2019. The PhD position is funded at the UK level, providing fees and stipend for a period of three years starting on 1 October 2020.

The studentship is fully-funded, therefore, only UK and EU students who meet the UK residency requirements as governed by the Education (Fees and Awards) Regulations 2007 are eligible to apply. As such, international students are not eligible to apply. For detailed information on residential eligibility guidelines, please visit the RCUK Training Grant Guide, Annex 1. Please note that if you are not a UK or EU student with an established residency in the UK, your application will not be reviewed. The residence eligibility criteria are satisfied in full if all three of the following conditions are met:

1. (a) the candidate is settled in the UK i.e. is ordinarily resident in the UK without being subject under the immigration laws to any restriction on the period for which they may stay in the UK;
2. (b) the candidate has been ordinarily resident in the UK and Islands for three years immediately prior to the date of start of their course;
3. (c) not been residing in the UK wholly or mainly for the purpose of full-time education, which does not apply to UK or EU nation

Enquiries by email, please. Closing deadline 1st May 2019.

Imperial College London and Royal Holloway, University of London are pleased to offer this BBSRC, fully-funded, four-year studentship starting in October 2019. Students enroll in a relevant Masters course in the first year followed by the PhD project for the remaining three years. 

Supervisors: Dr James Murray (Dept of Life Sciences, ICL) and Dr A William Rutherford

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.

How to apply:  Please contact James Murray on how to apply.

Closing date 12th March 2019

PhD Studentship based at Diamond, Harwell with Imperial College London.

Bacteria utilise membrane transporters as an essential mechanism for cell growth and survival, as well as to detoxify them from toxic compounds, including antibiotics. Primary active transporters harness the energy from ATP hydrolysis to transport molecules against a concentration gradient, while secondary active transporters use the energy stored in concentration gradients of protons or ions. Some secondary transporters utilise the Na+ gradient across membranes, created by other transporters that actively pump Na+ out of the cell, to drive the extrusion of solutes out of the cell. In this studentship, we want to understand the structural basis of antibiotic resistance by sodium-dependent secondary transporters including the role of Na+ in the process. We will also perform biochemical assays to characterise the ligand binding site and how Na+ regulates the function of the transporters. The work will refine our understanding on how these transporters operate since many of them are involved in multidrug resistance.

This project is fully funded for 3 years (3-year PhD), and will be based at the Imperial College London outstation at the Research Complex at Harwell, Oxfordshire and Diamond Light Source, Oxfordshire, jointly between the labs of Dr Konstantinos Beis and Dr Armin Wagner. The Research Complex at Harwell and Diamond Light Source are both located on the Rutherford Appleton site in South Oxfordshire. This site is ideally suited for structural biology research offering a highly multidisciplinary environment for structural biology with world leading facilities including Diamond, the electron Bio-Imaging Centre (eBIC), the Membrane Protein Laboratory (MPL) and CCP4 providing exceptional opportunities for synergies and collaborations. If you enjoy working as part of a highly motivated team, this position will offer you a great opportunity to contribute to this unique project and to work at a world-class facility.

The candidate must hold a BSc at 2:1 or better and MUST hold or expect a Masters degree at Merit level or better. The candidate must meet the Research Council residency criteria. It would ideally suit an outstanding biochemistry graduate with a strong interest in structural biology. The candidate must have molecular biology, protein production and purification experience. Experience with membrane proteins will be of an advantage. Full training will be provided in all necessary areas of protein biochemistry and structural work.

To be considered for this PhD, please send a motivation letter, CV and names of two referees to Dr Armin Wagner (armin.wagner@diamond.ac.uk) and Dr Konstantinos Beis (kbeis@imperial.ac.uk)

There is no closing date for applications and interviews will be conducted soon after suitable candidates have been identified.

Funding Notes:

The studentship is fully-funded which include a bursary (minimum £16,777 tax free) and fees (for UK/EU candidates only).

Academic Supervisor: Prof Vincent Savolainen, Dept of Life Sciences (Silwood Campus), ICL

CASE Partner: Unilever

Project Title: Metagenomics for the bioassessment of water bodies using mesocosms experiments 

Project Summary: Water bodies and their resident biodiversity are at risk from contaminants, disease agents, biological invasions and abiotic stressors. In the European Union, the Water Framework Directive is designed to provide the means to assess, monitor and manage water bodies in order to ensure safety, economic and natural resources sustainability. Traditionally, biological quality is assessed by obtaining abundance and diversity measures of existing communities using morphological methods. There is the need for conventional approaches to be supplemented with new technologies as they are timeconsuming, sometimes lacking accuracy and needing extensive taxonomic expertise. Here, we propose to explore new approaches for the assessment of water bodies, which benefit from the latest development in (eco)metagenomics, bioinformatic and chemical biology. Recent molecular advances, including the use of environmental DNA (eDNA) extracted from the water column, is revolutionizing this field, by generating novel high throughput data that could enable us to track and describe focal species as well as the wider food web within which they are embedded, and how they respond to external changes. The student will advance eDNA and metagenomic approaches using mesocosms available at Imperial College. Mesocosm-based approaches are increasingly being recognized as spanning the critical gap between field observations and lab experiments, by offering realistic levels of biocomplexity, whilst also affording a degree of control and replication of experimental conditions. The student will assemble artificial communities in the mesocosms and evolve how eDNA metabarcoding can recover presence and abundance of those organisms, employing cutting-edge molecular computational methods to better exploit metagenomic data and derive maximum value. Subsequently the student will test how eDNA can be used to uncover the impact that a range of chemical stressors may have on these artificial communities.

Funding Notes

This is a four-year, fully-funded industrial CASE studentship part of the BBSRC Imperial College London & Royal Holloway University of London Doctoral Training Partnership. The studentship covers: (i) a tax-free stipend at the standard Research Council rate (£17,009 per annum for 19/20AY), (ii) tuition fees at UK rate, and (iii) an annual financial contribution towards research and training. The industry partner will also provide financial support as agreed upon between the industry partner and the supervisor.

Eligibility & Application

To be eligible, candidates must either have, or expect to obtain, a BSc degree at 2.1 level or higher, or an equivalent qualification. This studentship is only available to UK and EU students who fulfil the three-year UK residency criteria. For additional information, please visit the Candidate Eligibility and Application Process sections. The deadline is Thursday, 2 May at 11:59pm UTC.

Supervisors: Dr Giorgio Gilestro (Dept of Life Sciences, ICL) and Dr Nikolai Windblicher (Dept of Life Sciences, ICL)

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

Funding Notes: This is a four-year, fully-funded industrial CASE studentship part of the BBSRC Imperial College London & Royal Holloway University of London Doctoral Training Partnership. The studentship covers: (i) a tax-free stipend at the standard Research Council rate (£17,009 per annum for 19/20AY), (ii) tuition fees at UK rate, and (iii) an annual financial contribution towards research and training. 

Eligibility & Application: To be eligible, candidates must either have, or expect to obtain, a BSc degree at 2.1 level or higher, or an equivalent qualification. This studentship is only available to UK and EU students who fulfil the three-year UK residency criteria. For additional information, please visit the Candidate Eligibility and Application Process sections. The deadline is Thursday, 2 May at 11:59pm UTC.

Supervisors: Dr James Murray (Dept of Life Sciences, ICL) and Dr A William Rutherford

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.

Funding Notes: This is a four-year, fully-funded industrial CASE studentship part of the BBSRC Imperial College London & Royal Holloway University of London Doctoral Training Partnership. The studentship covers: (i) a tax-free stipend at the standard Research Council rate (£17,009 per annum for 19/20AY), (ii) tuition fees at UK rate, and (iii) an annual financial contribution towards research and training. 

Eligibility & Application: To be eligible, candidates must either have, or expect to obtain, a BSc degree at 2.1 level or higher, or an equivalent qualification. This studentship is only available to UK and EU students who fulfil the three-year UK residency criteria. For additional information, please visit the Candidate Eligibility and Application Process sections. The deadline is Thursday, 2 May at 11:59pm UTC.

Supervisors: Dr Marina Kuimova (Dept of Chemistry, ICL) & Prof Ramon Vilar (Dept of Chemistry, ICL)

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. 

Funding Notes: This is a four-year, fully-funded industrial CASE studentship part of the BBSRC Imperial College London & Royal Holloway University of London Doctoral Training Partnership. The studentship covers: (i) a tax-free stipend at the standard Research Council rate (£17,009 per annum for 19/20AY), (ii) tuition fees at UK rate, and (iii) an annual financial contribution towards research and training. 

Eligibility & Application: To be eligible, candidates must either have, or expect to obtain, a BSc degree at 2.1 level or higher, or an equivalent qualification. This studentship is only available to UK and EU students who fulfil the three-year UK residency criteria. For additional information, please visit the Candidate Eligibility and Application Process sections. The deadline is Thursday, 2 May at 11:59pm UTC.