Dr Andrew Peden
Room: D06 Florey building
Brief career history
Constitutive secretion is a conserved process required for the delivery of newly synthesised proteins and lipids to plasma membrane as well as the exocytocis of extracellular factors such as cytokines, lipoproteins and antibodies. My lab is interested in identifying and characterising the pathways and machinery involved in constitutive secretion.
Elucidating the post-Golgi pathways and machinery required for constitutive secretion
2) To identify and characterise novel machinery required for post-Golgi trafficking and antibody secretion
Very little is known about the machinery required for budding, transporting, docking and fusing post-Golgi transport vesicles. To identify this machinery we are using two approaches. Firstly we are using a screening approach (RNAi or chemical) where we will make use of our novel secretion assays in mammalian and Drosophila cell lines. In the second approach we plan to use proteomics to quantify changes in protein expression associated with plasma cell differentiation.
Figure 2. Plasma cells secreting antibodies (nuclei are shown in blue and the secreted antibody (IgM) in green).
I have been actively involved in teaching throughout my academic career and have taught undergraduate and postgraduate students. In 2015 I obtained my Postgraduate Certificate in Learning and Teaching from the University of Sheffield and became a Fellow of The Higher Education Academy.
In 2013 I developed an innovative practical which demonstrates how basic molecular and cell biology underpin the diagnosis and treatment of disease. In the practical the students make Herceptin (Trastuzumab) and use it to diagnose HER2 positive cells.
Undergraduate and postgraduate taught modules
Title: Developing novel biosensors for monitoring antibody production in CHO cells
Supervisor: Dr Andrew Peden
Funding status: This is a BBSRC-funded Industrial CASE PhD studentship and is full time for four years. The stipend will be £17,553.00 per annum. Applicant eligibility criteria for the studentship can be found at: www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/ and you must identify that you fit these criteria prior to application.
The biopharmaceutical market is valued at over 100 billion dollars per year with the majority of therapeutic antibodies being manufactured in Chinese Hamster Ovary (CHO) cells. However, the process of generating monoclonal antibody (mAb) producing cell lines suitable for commercial manufacture remains challenging, time consuming and costly.
The cellular pathways underpinning antibody production in CHO cells have been extensively studied over the past 10 years; however, it is still unclear which pathways are most important for this process (protein folding, protein transport and cell stress). The aim of this PhD is to facilitate a deeper understanding of CHO mAb production cell lines by investigating the intracellular phenotypes of CHO cell lines which are producing and secreting monoclonal antibodies. Using the knowledge gained we aim to define a phenotypic fingerprint which correlates with favourable manufacturing and product quality characteristics. Once these fingerprints have been defined, a series of novel fluorescent tools for monitoring them will be developed and applied to our cell line development platform to allow screening for optimal mAb producing cell lines in the earliest stages of cell line development.
This project will provide training in advanced mammalian cell culture, fluorescence microscopy, flow cytometry and access to state of the art, high-throughput, automated systems for cell culture (Berkeley Lights Beacon) and phenotypic analysis (Intellicyt iQue) in place at the GSK laboratories.
The studentship is available starting in October 2017. This project is collaboration between Dr Andrew Peden at the University of Sheffield and Dr Robyn Emmins, GSK Biopharmaceutical Process Research, Stevenage. Candidates should have a strong academic degree in the biological sciences. The successful candidate will be highly motivated, work effectively in a team setting and be interested in cell biology, protein trafficking and technology development.
For further information about all studentship projects within the department and how to apply, see our PhD Opportunities page:
- Gordon DE, Chia J, Jayawardena K, Antrobus R, Bard F & Peden AA (2017) VAMP3/Syb and YKT6 are required for the fusion of constitutive secretory carriers with the plasma membrane. PLOS Genetics, 13(4). View this article in WRRO
- Zlatic SA, Grossniklaus EJ, Ryder PV, Salazar G, Mattheyses AL, Peden AA & Faundez V (2013) Chemical-genetic disruption of clathrin function spares adaptor complex 3-dependent endosome vesicle biogenesis. Molecular Biology of the Cell, 24(15), 2378-2388.
- Jacob A, Jing J, Lee J, Schedin P, Gilbert SM, Peden AA, Junutula JR & Prekeris R (2013) Rab40b regulates trafficking of MMP2 and MMP9 during invadopodia formation and invasion of breast cancer cells. Journal of Cell Science, 126(20), 4647-4658.
- Kent HM, Evans PR, Schäfer IB, Gray SR, Sanderson CM, Luzio JP, Peden AA & Owen DJ (2012) Structural Basis of the Intracellular Sorting of the SNARE VAMP7 by the AP3 Adaptor Complex. Developmental Cell, 22(5), 979-988.
- Miller SE, Sahlender DA, Graham SC, Höning S, Robinson MS, Peden AA & Owen DJ (2011) The molecular basis for the endocytosis of small R-SNAREs by the clathrin adaptor CALM. Cell, 147(5), 1118-1131.
- Gordon DE, Bond LM, Sahlender DA & Peden AA (2010) A targeted siRNA screen to identify SNAREs required for constitutive secretion in mammalian cells. Traffic, 11(9), 1191-1204.
- Wendler F, Gillingham AK, Sinka R, Rosa-Ferreira C, Gordon DE, Franch-Marro X, Peden AA, Vincent JP & Munro S (2010) A genome-wide RNA interference screen identifies two novel components of the metazoan secretory pathway. EMBO Journal, 29(2), 304-314.
- Gordon DE, Mirza M, Sahlender DA, Jakovleska J & Peden AA (2009) Coiled-coil interactions are required for post-Golgi R-SNARE trafficking. EMBO Reports, 10(8), 851-856.