Molecular principles for the biogenesis and assembly of α-carboxysomes

Description

Organelles confine specific biochemical pathways within the cell to enhance metabolic efficiency, alleviate metabolic crosstalk, and facilitate spatiotemporal regulation of sequestered pathways. Their naturally-occurring building and functional principles have inspired the synthetic engineering of self-assembling organelles and the redesign of new structures, with the potential for widespread biotechnological and biomedical applications.

The carboxysome is a bacterial microcompartment that functions as a primitive protein-based organelle for COfixation1. It encapsulates the key CO2-fixing enzymes, Rubisco and carbonic anhydrase, within a semi-permeable protein shell. This elaborate architecture provides elevated CO2 levels around Rubisco for enhanced carbon fixation, thus playing an important role in the global carbon cycle.

Aims:

Builds on our recent research breakthroughs2-10, this PhD project is aimed at deciphering in depth the molecular principles underlying the biosynthesis, assembly, and regulation of carboxysomes, using multidisciplinary techniques in molecular genetics, biochemistry, microscopy, structural biology, and synthetic biology. The study will offer advanced knowledge about how carboxysomes are generated and functionally modulated in cells to fulfil functions and the structural variability of carboxysomes to ensure environmental adaptation. Our long-term goal is to provide the framework for the bioengineering of functional and modifiable metabolic organelles and the development of new nanomaterials for diverse biotechnological applications, with the aim of addressing the grand challenges of climate change, food and energy security, and therapeutics.

Training:

This project builds on a truly multidisciplinary collaboration between the world-leading laboratories at the University of Liverpool and Newcastle University, by combining interdisciplinary skills ranging from microbiology, cell biology, biochemistry, synthetic biology, to super-resolution fluorescence imaging and cryo-electron microscopy. The student will have access to state-of-the-art facilities at the host institutions, including Cell Imaging, cryo-electron microscopy, Synthetic Biology, Proteomics, Metabolomics, Genomics, and Computational Modelling. The student will spend three months and have regular visits in co-supervisors’ labs for high-resolution microscopy and data process. These will provide a fantastic and vibrant training environment for the student. Moreover, external collaborations of the host labs in the UK, EU, US, Australia, and Asia will add extra value to the student’s training. Collectively, this project will provide the student with extensive training in interdisciplinary techniques, project management, communications, and collaborative networking, which are vital for their research independence, international vision, and career development.

Selection Requirements:

We invite applications from highly motivated students in molecular biology, biochemistry, microbiology, biotechnology, or a related subject. The applicants should hold, or be about to obtain, a First or Upper Second class Honours degree, or the equivalent qualification gained outside the UK. As competition is fierce, many of our applicants also hold a Masters-level qualification. The applicants should have a demonstrated ability to work in a laboratory environment.

To apply for the studentship, before completing the How to Apply section below, please send your CV and a cover letter with contact information of two referees to Prof Luning Liu (). You are encouraged to contact by email to discuss the project details at early as possible. Detailed research activities are available on the lab website: www.luningliu.org.

HOW TO APPLY

Applications should be made by emailing  with:

·        a CV (including contact details of at least two academic (or other relevant) referees);

·        a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, 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;

·        copies of your relevant undergraduate degree transcripts and certificates;

·        a copy of your IELTS or TOEFL English language certificate (where required);

·        a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to . A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to 

The deadline for all applications is 12noon on Monday 9th January 2023.

Availability

Open to students worldwide

Funding information

Funded studentship

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

Supervisors

References

1. Liu. 2022 Trends in Microbiology 30:567;
2. Ni et al. 2022 Nature Communications 13:4299;
3. Yang et al. 2022 Nature Communications 13:2920;
4. Chen et al. 2022 Plant Cell accepted;
5. Sun et al. 2022 mBio 13:e0362921;
6. Chen et al. 2022 ACS Synth Biol 11:154;
7. Huang et al. 2022 Biomacromolecules 23:4339;
8. Fang et al. 2021 Proc Natl Acad Sci U S A 118:e2101632118;
9. Li et al. 2020 Nature Communications 11:5448;
10. Huang et al. 2020 Proc Natl Acad Sci USA 117:17418;