Dr Andrew Peden

Andrew Peden

Lecturer
Department of Biomedical Science
The University of Sheffield
Western Bank, Sheffield
S10 2TN
United Kingdom

Room: D06 Florey building
Telephone: 0114 222 2312
Email: a.peden@sheffield.ac.uk

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General

Brief career history

  • 2012-present: Lecturer, department of Biomedical Science, the University of Sheffield
  • 2006-2010: Principal Investigator, University of Cambridge (MRC Career Development Award).
  • 2001-2005: Postdoctoral fellow, Genentech Inc.
  • 2000-2001: Postdoctoral fellow, Stanford University (Wellcome Trust Research Fellowship).
  • 1995-1999: PhD, University of Cambridge.
  • 1991-1995: BSc., University of Edinburgh.

Research interests

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.

Professional activities

  • Fellow of the Higher Education Academy (FHEA)
  • Editor for BMC Cell biology
  • Reviewer for BBSRC and MRC

Full publications list

Research

Elucidating the post-Golgi pathways and machinery required for constitutive secretion

Constitutive secretion is required for many biologically important processes, such as inflammation (cytokine secretion), adaptive immunity (IgG secretion), tissue remodelling (extracellular matrix secretion) and cholesterol homeostasis (lipoprotein particle secretion). Perturbations in the secretion of these factors can cause disease. For example dysregulation of antibody secretion plays a significant role in the development of diseases such Amyloidosis, Macroglobulinemia and Monoclonal Gammopathies. Thus having the ability to modulate the secretion of various cellular factors has significant therapeutic potential.

My lab has 3 main aims:

Peden lab: Group focus


1) To elucidate the role of SNAREs in constitutive secretion

SNAREs are a family of proteins required for the fusion of membranes and there are 38 encoded in the human genome. Each SNARE is localised to a specific compartment within the cell and required a defined set of fusion steps. However, it is not known which SNAREs are required for the fusion of secretory vesicles with the plasma membrane. To address this we have developed novel assays for measuring constitutive secretion and have used them in conjunction with targeted siRNA screens in both mammalian and Drosophila based systems. We have shown that in mammals the post-Golgi SNAREs SNAP29 and STX19 and are required for constitutive secretion. SNAP29 is mutated in the human disorder CEDNIK so our work may help shed light on the molecular details of this disease.

Many questions remain regarding the role of SNAREs in constitutive secretion. For example, how are the functions of SNAP29 and STX19 coordinated, how is constitutive secretion regulated, how are SNAREs packaged into post-Golgi secretory carriers. We are addressing these questions using live cell imaging, secretion assays, proteomics and structural based approaches.

Movie showing RPE-1 cells secreting the GFP tagged protein we use to measure secretion. The tubular structures emanating from the centre of the cells are secretory carriers which will eventually fuse with the plasma.

Figure 1 (a)



Movie showing RPE-1 cells secreting the GFP tagged protein we use to measure secretion.

The tubular structures emanating from the centre of the cells are secretory carriers which will eventually fuse with the plasma.


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

Figure 2. Plasma cells secreting antibodies  (nuclei are shown in blue and the secreted antibody (IgM) in green).


3) To understand the molecular interactions required for post-Golgi trafficking and secretion

To elucidate the molecular interactions involved in post-Golgi trafficking and secretion we are tacking a structural approach in collaboration with Professor David Owen.

We are particularly interested in understanding how post-Golgi SNAREs are packaged into transport vesicles. We have recently shown that the clathrin coated vesicle protein CALM directly binds to the coiled-coil domains of the R-SNAREs VAMPs 2/3/8 and facilitates their internalisation.

Collaborators

  • David James (University of Sheffield)
  • Mark Collins  (University of Sheffield)
  • Bazbek Davletov (University of Sheffield)
  • Luke Chamberlain (University of Strathclyde)
  • Clare Futter  (University College London)

Funding

  • BBSRC
  • MRC
  • Medimmune
  • UCB

Figure 3

Teaching

Teaching experience

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

Level 2:

  • BMS238 Cell and Molecular Biology (Coordinator)

Level 3:

  • BMS349 Extended Library Project
  • BMS369 Laboratory Research Project
Opportunities

PhD Studentship

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.

Project Description

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 informal enquiries about this project, please feel free to contact Andrew Peden

Email: a.peden@sheffield.ac.uk or Dr Robyn Emmins (robyn.a.emmins@gsk.com)

For further information about all studentship projects within the department and how to apply, see our PhD Opportunities page:

PhD Opportunities

Selected publications

Journal articles