Don't miss our weekly PhD newsletter | Sign up now Don't miss our weekly PhD newsletter | Sign up now

  Optimising protein production from high density Bacillus subtilis cultures by suppressing autolysis


   Institute for Cell and Molecular Biosciences

This project is no longer listed on FindAPhD.com and may not be available.

Click here to search FindAPhD.com for PhD studentship opportunities
  Dr H Strahl von Schulten  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

The Gram-positive bacterium Bacillus subtilis is a highly amenable industrial production host used to produce numerous commercially valuable enzymes. The prominent role of B. subtilis in industrial production of recombinant proteins is based on the easy with which its genome can be engineered (more recently including the CRISPR technology), and the ability to produce high yields of protein by secretion directly to the extracellular medium thereby facilitating cost-effective purification. In addition to being an industrial production host, B. subtilis is among the best studied bacterial model organism. One of the reasons for this is its characteristic cell differentiation processes that result in distinct sub-populations of cells that enter distinct cellular differentiation pathways. However, the ability to differentiate into district sub-population has negative consequences for the function of B. subtilis as a protein production host as not all of the resulting cell types contribute to the protein production process.

In this joint biotechnology-themed research project between Newcastle University and DSM, the student will determine how the fitness of B. subtilis, in terms of its energy status during industry-like fermentation conditions, can be optimised for improved protein production. A specific focus will be on studying the cell autolytic process, which affects a significant proportion of the cell population and thus reduces the protein production yield. How the fermentation conditions can be optimised to minimise autolysis, and how the production host can be re-engineered to suppress the autolytic process will be studied with the ultimate goal to improve recombinant protein production.

The student will enjoy an exceptionally broad training in state-of-the-art techniques in molecular and cellular biology including molecular cloning and high end microscopy, and biotechnological methods including production host optimisation, fermentation, and recombinant protein production. The PhD programme will be carried out at the Centre for Bacterial Cell Biology (Newcastle University), a world-class research centre with focus on microbiology. Research stays with the industrial partner at the DSM Biotechnology Center (Delft, the Netherlands) are foreseen providing the student with work experience in an industrial research environment.

For further information see the website: https://www.ncl.ac.uk/camb/

To apply
Please complete the online application form and attach a full CV and covering letter. Informal enquiries may be made to [Email Address Removed]

Funding Notes

This is a 4 year BBSRC CASE studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£14,777 for 2018-19). There is the possibility of an uplift to the stipend from the industrial sponsor. The PhD will start in October 2019. 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. There are 2 stages to the application process.

References

Te Winkel JD, Gray DA, Seistrup KH, Hamoen LW, Strahl H. (2016) Analysis of antimicrobial-triggered membrane depolarisation using voltage sensitive dyes. Front Cell Dev Biol 4:29.