Engineering pathways and biosensor systems for production and detection of chemical compounds in bacteria
Lab rotation project description
The use of biotechnology for the sustainable production of chemicals and materials, the synthesis of which has traditionally depended heavily on the fossil fuel-based chemical industry, is becoming increasingly important. The development of microbial strains for this purpose can be improved through rational metabolic engineering involving synthetic and systems biology techniques. In the followed PhD project, the metabolically versatile organism Cupriavidus necator, capable of using H2 and CO2 as its sole sources of energy and carbon, will be used to identify potentially interesting biotechnological products through examination of the metabolic network and to improve such products production through metabolic engineering.
The mini project will serve as an introduction to the available gene tools to be deployed in C. necator. The student will: (i) receive a safety induction to cover safe laboratory practice within the confines of SBRC laboratories and equipment within the Centre; (ii) be trained in the use of cultivation of E. coli and C. necator; (iii) learn pathway design and assembly for metabolite production; (iv) be trained in fluorescence based assays for developing biosensor systems; (v) be introduced in analytical techniques for gas and metabolite analysis, such as HPLC, GC, and MS.
LR1, LR2 and LR3
Linked PhD Project Outline
The production of chemicals from renewable sources is a key for a sustainable future. Various compounds can be produced by bacteria and yeast carrying synthetic metabolic pathways assembled of multiple genes derived from other organisms. Lithoautotropic bacteria such as Cupriavidus necator possess the attractive property of converting carbon dioxide into organic compounds using hydrogen as a sole energy source. The PhD project will be aimed at engineering C. necator to produce important platform chemicals such as isoprene, propylene, butadiene, and isobutene, and to develop sensory systems for detection of these compounds and their intermediates. Combinatorial transcriptional engineering and genetically encoded metabolic switch strategies will be used for optimisation of synthetic metabolic pathways. Development and optimisation of the aerobic C1 gas fermentation process for bioproduction will play important part in the project.
The ability of autotrophic organism such as C. necator to fix carbon dioxide will present an opportunity to utilise this ‘greenhouse gas’ as an inexpensive substrate for chemical production. The use of this microorganism as a production platform will provide an exciting prospect for bio-based chemical production.
The project will be carried out within the BBSRC/EPSRC Synthetic Biology Research Centre (SBRC). The successful candidate will join a highly motivated and well-funded team of research scientists dedicated to the exploitation of industrial important microorganisms. The SBRC is located in state-of-the-art facilities in the £25M Centre for Biomolecular Sciences (http://www.nottingham.ac.uk/cbs. Centre’s set-up will provide training in a unique multidisciplinary environment. The project will include a strong wet component, for which the student will require to become familiar with an array of experimental techniques. The study will allow for training in a unique multidisciplinary environment, incorporating systems and synthetic biology, metabolic engineering, gas fermentation, biochemical and biophysical analytical techniques. The project will also include an exciting dry component, which will require a good grasp of general metabolic pathway design and analysis techniques. It is also anticipated that the nature of how SBRC is organized will provide good opportunities for building new academic and industrial links.