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Understanding and synthetic engineering of bacterial organelles for metabolic enhancement

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  • Full or part time
    Prof LN Liu
    Dr T Howard
    Dr Jon Marles-Wright
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

With the rapid growth of the global population, the demand for food and energy is dramatically increasing. There is an urgent need to develop innovative strategies, by taking advantage of modern biotechnology, to enhance agricultural production. The single-cell photosynthetic bacteria, cyanobacteria, account for over 25% of the global carbon fixation, thanks for their powerful CO2-concentrating machinery. This unique system comprises proteins embedded in cell membranes to pump CO2 and bicarbonate through cell membranes and accumulate them in the cell, and the central CO2-fixing machines, named carboxysomes, to fix CO2. Advanced understanding of the formation and regulation of carboxysomes offers great opportunities for the construction of metabolic organelles using synthetic biology. For example, introducing functionally active carboxysomes into plants is considered as a promising strategy for boosting photosynthesis and crop yields. It will also inspire the development of new nanomaterials and protein scaffolds for biotechnological applications, e.g. enhancing cell metabolism and molecule delivery.

This PhD project will address how carboxysomes are synthesised and formed in cyanobacterial cells and how they define their architectures for functional and physiological regulation. Harnessing the knowledge, this project will develop cell-free systems and microscopic screening to reconstitute carboxysome structures in other organisms and in vitro, with the capability of modulating their formation and functions. The long-term goal is to provide solutions for bioengineering and biotechnology, to meet the grand challenges in food and energy security.

This project represents joint scientific efforts of the Liu Lab at the University of Liverpool (UoL) the Howard Lab and Marles-Wright Lab at Newcastle, by combining interdisciplinary skills and training ranging from molecular genetics, cell biology, biochemistry, microbiology to biophysics, cryo-electron microscopy, and synthetic biology. The student will be based in the Liu lab (www.luningliu.org) by working with other Postdocs and PhDs, with the opportunity to spend 3 months and regular visits in the Howard Lab and Marles-Wright Lab at Newcastle and have a 3-month placement with industrial partners and Royal society Publishing Group. The UoL provides a unique combination of facilities and expertise for this project, including Cell Imaging, GeneMill, Proteome Research, Computational Modelling and Metabolomics. Training in all aspects of the project will be provided with access to state-of-the-art infrastructure in IIB and with leading collaborators in the UK, Europe, Australia, US, and China, which means that there will be good opportunities for developing a strong scientific network and the student’s career development.

HOW TO APPLY

Applications should be made by emailing [Email Address Removed] with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – clearly stating your first choice project, and optionally 2nd and 3rd ranked projects, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University. Applications not meeting these criteria will be rejected.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to [Email Address Removed]



Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.

References

Structural mechanism of the active bicarbonate transporter from cyanobacteria. Nature Plants, 2019, 5(11): 1184-1193

Single-organelle quantification reveals the stoichiometric and structural variability of carboxysomes dependent on the environment. Plant Cell, 2019, 31(7): 1648-1664

Roles of RbcX in carboxysome biosynthesis in the cyanobacterium Synechococcus elongatus PCC7942. Plant Physiology, 2019, 179(1): 184-194

Engineering and modulating functional cyanobacterial CO2-fixing organelles. Frontiers in Plant Science, 2018, 9: 739

Direct characterization of the native structure and mechanics of cyanobacterial carboxysomes. Nanoscale, 2017, 9(30): 10662-10673

Light modulates the biosynthesis and organization of cyanobacterial carbon fixation machinery through photosynthetic electron flow. Plant Physiology, 2016, 171(1): 530-541


Rapid, Heuristic Discovery and Design of Promoter Collections in Non-Model Microbes for Industrial Applications. ACS Synthetic Biology 2019, 8(5), 1175-1186

Design of Experiments Methodology to Build a Multifactorial Statistical Model Describing the Metabolic Interactions of Alcohol Dehydrogenase Isozymes in the Ethanol Biosynthetic Pathway of the Yeast Saccharomyces cerevisiae. ACS Synthetic Biology 2018, 7(7), 1676-1684

Structural characterization of encapsulated ferritin provides insight into iron storage in bacterial nanocompartments. Elife, 2016, 5: e18972

Structural Insight into the Clostridium difficile Ethanolamine Utilisation Microcompartment. PLoS One 2012, 7, e48360.

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