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
Elucidating the molecular function of SNAP29 a gene mutated in CEDNIK syndrome
Funding status: Competition funded project European/UK students only
This project is eligible for a department scholarship. These scholarships are awarded on a competitive basis – find out more on our funding webpage.
CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis and keratoderma) syndrome is a rare fatal disease caused by the loss of SNAP29. SNAP29 is member of a family of proteins required for membrane transport and specifically vesicle fusion. We have rshown that SNAP29 is required for the fusion of secretory vesicles with the plasma membrane. Thus, our work suggests that CEDNIK syndrome may be in part be caused by a defect in constitutive secretion.
The aim of this project is to elucidate the molecular details of how SNAP29 functions. Specifically the project will:
1) Determine how SNAP29 is targeted and packaged into post-Golgi vesicles.
2) Identify proteins required for coordinating SNAP29s function. This project will use a combination of super-resolution microscopy, proteomics and CRISPR/Cas9 based techniques.
This project has the potential to elucidate the molecular pathologies which underpin CEDNIK syndrome.
Keywords: Biochemistry, Cell Biology / Development, Genetics, Molecular Biology
For informal enquiries about the project or application process, please feel free to contact me.
Elucidating the signalling pathways important for plasma cell biology and antibody secretion
Co-supervisor: Dr Mark Collins
Funding status: This project is also open to self funded students
Plasma cells are the antibody secreting cells of the immune system thus are vital for fighting infection. However, dysregulation of plasma cell function is linked to a broad range of disease from Lupus to multiple myeloma. At present, it is not known how plasma cell differentiation and homeostasis is regulated.
The aim of this PhD project is to identify the key signaling pathways critical for this process. To identify these pathways we will use a combination of cutting edge in vitro cell culture models and novel mass-spectrometry based approaches. Once key pathways have been identified, we will manipulate them using chemical and genetic based approaches and determine how this affects plasma cell biology. In the long term, this information may help in the development of novel drugs for regulating plasma cell function in vivo. This project represents an exciting training opportunity where the student will become an expert in advanced proteomics, mechanistic cell biology and immunology.
Keywords: Biochemistry, Bioinformatics, Biotechnology, Cell Biology / Development, Immunology, Molecular Biology, Bioinformatics
For further information on all studentship projects, within the department, and how to apply, see our PhD Opportunities page:
- Jonker CTH, Galmes R, Veenendaal T, Ten Brink C, Van Der Welle REN, Liv N, De Rooij J, Peden AA, Van Der Sluijs P, Margadant C & Klumperman J (2018) Vps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin-dependent functions. Nature Communications, 9(1). View this article in WRRO
- Rust A, Doran C, Hart R, Binz T, Stickings P, Sesardic D, Peden AA & Davletov B (2017) A cell line for detection of botulinum neurotoxin type B. Frontiers in Pharmacology, 8, 796-796. View this article in WRRO
- 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
- Dickens JA, Ordonez A, Chambers JE, Beckett AJ, Patel V, Malzer E, Dominicus CS, Bradley J, Peden AA, Prior IA, Lomas DA & Marciniak SJ (2016) The endoplasmic reticulum remains functionally connected by vesicular transport after its fragmentation in cells expressing Z-α1-antitrypsin. The FASEB Journal, 30(12), 4083-4097. View this article in WRRO
- Chiaruttini G, Piperno GM, Jouve M, De Nardi F, Larghi P, Peden AA, Baj G, Müller S, Valitutti S, Galli T & Benvenuti F (2016) The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells. Cell Reports, 14(11), 2624-2636. View this article in WRRO
- Jubrail J, Morris P, Bewley MA, Stoneham S, Johnston SA, Foster SJ, Peden AA, Read RC, Marriott HM & Dockrell DH (2015) Inability to sustain intraphagolysosomal killing of Staphylococcus aureus predisposes to bacterial persistence in macrophages. Cellular Microbiology, 18(1), 80-96. View this article in WRRO
- Gokhale A, Mullin AP, Zlatic SA, Easley CA, Merritt ME, Raj N, Larimore J, Gordon DE, Peden AA, Sanyal S & Faundez V (2015) The N-Ethylmaleimide-Sensitive Factor and Dysbindin Interact To Modulate Synaptic Plasticity. Journal of Neuroscience, 35(19), 7643-7653.
- Matheson NJ, Peden AA & Lehner PJ (2014) Antibody-Free Magnetic Cell Sorting of Genetically Modified Primary Human CD4+ T Cells by One-Step Streptavidin Affinity Purification. PLoS ONE, 9(10). 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.