Design, construction and testing of recombinant protein production systems for industrial biotechnology applications.

The production of recombinant biopharmaceuticals, e.g., antibody fragments and growth hormones, is a billion-dollar industry, with many therapeutic proteins being expressed in the bacterium Escherichia coli [1]. Most of the E. coli expression systems used for recombinant protein production (RPP) were constructed in the last century and many of them require an inducer molecule, such as IPTG (isopropyl-β-D-thiogalactoside), to switch on expression of the target protein [1]. However, such inducer molecules can be toxic to the cell, unstable and are extremely expensive, with IPTG exceeding £52000 per kg. To reduce the cost of RPP, we have used synthetic biology to engineer completely new E. coli RPP expression systems, which use cheap and freely available inducer molecules, such as nitrate and urea [2,3]. This was achieved by using different transcription factors to control the expression of industrially relevant targets protein. Thus, using our systems, we were able to show that proteins, such as human growth hormone (hGH), could be expressed to comparable levels seen with standard RPP systems. As many of our inducer molecules are freely available, this innovation demonstrated that controlled, high level RPP can be easily achieved using unconventional inducers (e.g., garden fertilizers and even urine!), drastically cutting the cost of RPP in areas of the world where infrastructure and resources are limited.

As the genomes of bacteria, such as E. coli, contain a multitude of transcription factors that respond to different environmental signals the goal of this project will be to design, construct, and test new recombinant protein production systems, that utilise and respond to cheap and freely available inducer molecules. This project will provide extensive training in many essential molecular biology, biochemical and biotechnology related techniques.

References: *Research from the supervisor’s laboratory

1*) Browning, D.F., Godfrey, R.E., Richards, K.L., Robinson, C. and Busby, S.J.W. (2019) Exploitation of the Escherichia coli lac operon promoter for controlled recombinant protein production. Biochemical Society Transactions. 47:755-763.  

2*) Hothersall, J., Lai, S., Zhang, N., Godfrey, R.E., Ruanto, P., Bischoff, S., Robinson, C., Overton, T.W., Busby, S.J.W, Browning, D.F. (2022). Inexpensive protein overexpression driven by the NarL transcription activator protein. Biotechnology and Bioengineering. 119(6):1614-1623.

3*) Hothersall, J., Osgerby, A., Godfrey, R.E., Overton, T.W., Busby, S.J.W and Browning, D.F. (2022) New vectors for Urea-Inducible Recombinant Protein Production. New Biotechnology. In press

Supervisors

Dr Douglas F Browning

PhD programmes are for those who are seeking to develop greater in-depth knowledge in a specific area. Completing this level of study is about making an original contribution to knowledge, making new discoveries, and developing lifelong skills. 

At Aston University, our Engineering and Physical Sciences PhD programmes will provide all the support and facilities you will need to develop into a leading researcher in your chosen field. You will be welcomed into a supportive community with a shared enthusiasm for original research, where diversity and multidisciplinary is championed.

Person Specification

Candidates should have been awarded, or expect to achieve, EITHER:

• A Bachelors degree in a relevant subject with an award of First Class or 2.1. 

OR 

• A Bachelors degree in a relevant subject with an award of First Class or 2.1, and a Masters degree in a relevant subject with an award of Merit or higher.

Qualifications from other countries which are considered by Aston University to be equivalent to that described above will be eligible to apply.

Submitting an application

We can only consider applications that are complete and have all supporting documents. Applications that do not provide all the relevant documents will be automatically rejected. Your application must include: 

1. English language copies of the transcripts and certificates for all your higher education degrees, including any Bachelor's degrees.
    
2. A Research Statement detailing your understanding of the research area, how you would approach the project, and a brief review of relevant literature. Be sure to use the title of the research project you are applying for. There is no set format or word count. 
    
3. A personal statement which outlines any further information which you think is relevant to your application, such as your personal suitability for research, career aspirations, possible future research interests, and further description of relevant employment experience. 
    
4. Two academic referees who can discuss your suitability for independent research. References must be on headed paper, signed, and dated no more than 2 years old. At least one reference should be from your most recent University. You can submit your references at a later date if necessary. 
    
5. Evidence that you meet the English Language requirements. If you do not currently meet the language requirements, you can submit this at a later stage. 
    
6. A copy of your passport. Where relevant, include evidence of settled or pre-settled status.

Interviews

Interviews will be conducted online via Microsoft Teams. If you are shortlisted, you will be contacted directly with details of the interview.  

Studying for a PhD is a great route into academia and industries that are centred on research and innovation. Areas with a demand for very high level and specialised research skills often demand PhDs.

In addition to this specialist knowledge, a PhD education will help you to develop a set of valuable transferable skills. The very nature of studying an intensive research degree will enable you to become a team player, develop problem-solving skills, analytical thinking, and advanced presentation and communication skills.

The variety of PhD project topics at Aston means that the destinations of our graduates vary substantially. Some choose to continue into academia, at either Aston or other leading institutions, while others go onto use their newly acquired skills in a range of research, healthcare, industry, or charitable fields. When selecting your chosen PhD path at Aston, your supervisor will be able to provide you with relevant career opportunities that could be available to you in your specialist area.