Hypothesis: The mitochondrial organellar compartment is responsible for balanced metabolism and ATP production plus generates reactive oxygen species and mediates apoptosis regulation – defining an environment that controls synthesis of recombinant biopharmaceuticals in CHO cells, the industry gold standard “cell factory” for manufacture of economically- and societally-valuable therapeutic medicines. The number and functional status of mitochondria in a CHO cell will be critical determinants of yield, specific productivity and quality of secreted recombinant proteins. The CHO cell mitochondrial compartment presents a logical target for engineering (environmental and genetic) to generate more efficient CHO cell growth, specific productivity and survival for manufacture.
Project Description: The accepted wisdom is that CHO cells exhibit inefficient metabolism, with inappropriately high glycolytic metabolism early in culture prior to switching to more efficient mitochondrially-localised ATP generation (Torres et al 2024 Metab Eng 88: 39). The “sector” identifies that mitochondrial compartment status is a strong indicator of, and potential target for, increasing the efficiency of CHO cells in biomanufacture (Chakrabarti et al 2022 mAbs 14: 2020081). With this perception, the lack of clear information about the status of mitochondria in CHO cells is astounding. How many mitochondria per CHO cell, how heterogeneous are populations, how is mitochondrial replication co-ordinated with cell division and environmental conditions, how are mitochondrial sensing functions set (eg apoptosis) …. all are aspects that are outcomes of the interaction of hundreds of genes (encoded from both nuclear and mitochondrial DNA), yet we know little. The mitochondrial compartment offers a novel target with great potential for enhancement of the efficiency of CHO cell biomanufacturing.
Entry Requirements
Applicants should hold (or be about to obtain) a First or Upper Second class (2:1) UK honours degree, or international equivalent, in a relevant subject.
Application Guidance
Candidates must contact the primary supervisor before applying to discuss their interest in the project and assess their suitability.
Apply directly via this link: https://tinyurl.com/zycedema or on the online application portal, select BBSRC DTP PhD as the programme of study. You may apply for up to two projects within this scheme. To do so, submit a single online application listing both project titles and the names of both main supervisors in the relevant sections.
Please ensure that your application includes all required supporting documents:
Curriculum Vitae (CV)
Supporting Statement
Academic Certificates and Transcripts
Incomplete or late applications will not be considered. Further details are available on our website: BBSRC North West Doctoral Programme in Bioscience | Biology, Medicine and Health | The University of Manchester
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