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Regulation of clostridial solvent production by quorum sensing

Project Description

The genus Clostridium comprises a large group of strictly anaerobic and metabolically diverse spore-forming bacteria. It contains pathogens and producers of deadly toxins but also species of industrial importance (1). The latter include species such as Clostridium acetobutylicum or Clostridium beijernickii which are well known for their ability to convert sugars and starches into organic acids and solvents. During the first half of the last century, these bacteria were used for the large scale production of acetone and butanol, but today the classical AB (acetone-butanol) fermentation process is no longer economically viable. Thus, considerable efforts have been devoted to improving the organisms’ performance through metabolic engineering. Today’s efforts concentrate on sugar fermenting Clostridia and also species capable of growing on industrial waste gases. However, we are still lacking a detailed understanding of the organisms’ physiology and metabolism, including the mechanisms that govern timing and extent of solvent formation.

In previous work, we discovered a large number of quorum sensing systems in solvent-producing clostridia, which enable individual cells of a population to communicate with one another via diffusible signal molecules (2, 3). We have shown that many of these systems strongly influence the production acetone, butanol and ethanol, but the underlying molecular mechanisms remain unknown.

Project aims:
The overall aim of the proposed PhD project is to investigate and exploit clostridial cell-cell communication systems to improve production of biobutanol and other solvents. This will be achieved using a combination of modern omics approaches, classical physiological and biochemical studies, and state-of-the-art genetic engineering techniques (4). The objectives are to

(i) Establish the transcriptional, translational, and physiological changes occurring in QS mutants;
(ii) Identify the genes directly controlled by QS using RNAseq, ChIP-seq and/or GeF-seq;
(iii) Characterise identified key genes and there role in solvent formation (e.g. via CRISPR/Cas inactivation);
(iv) Exploiting the generated knowledge for the engineering of superior production strains.

The project thus operates at the interface of fundamental and applied research, providing ample opportunities to publish and build up a reputation in both of these areas. It offers training in anaerobic microbiology, advanced microbial genetics, next generation sequencing, transcriptomics, bioinformatics, handling and analysis of large data sets, interactions with mathematical modelling, molecular biology, batch and continuous fermentation systems, gas/liquid chromatography, and synthetic biology.
We are part of the BBSRC/ EPSRC Synthetic Biology Centre with strong links to other groups in the Biotech sector in Europe, the US, China and India, providing ample opportunity to take part in international conferences, workshops, and exchange programmes.

The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers.

Funding Notes

Home applicants should contact the supervisor to determine the current funding status for this project. EU applicants should visit the Graduate School webpages for information on specific EU scholarships View Website. International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University View Website.


1. Dürre, P (2014) Physiology and Sporulation in Clostridium. Microbiol Spectr., TBS-0010-2012.
2. Steiner E, Scott J, Minton NP and Winzer K (2012) An agr quorum sensing system that regulates granulose formation and sporulation in Clostridium acetobutylicum. Appl. Environ. Microbiol. 78, 1113-1122.
3. Kotte A-K et al. (2017) RNPP-type quorum sensing regulates solvent formation and sporulation in Clostridium acetobutylicum. bioRxiv
4. Li Q et al. (2016) CRISPR-based genome editing and expression control systems in Clostridium acetobutylicum and Clostridium beijerinckii. Biotechnol. J. 11, 961-72.
5. Liew F et al. ( 2017) Metabolic engineering of Clostridium autoethanogenum for selective alcohol production. Metabolic Engineering. 40, 104-114.

Related Subjects

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FTE Category A staff submitted: 90.86

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