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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Cell Biology and Cancer


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

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.

Project Description

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

References:

  • Gordon D.E., Bond L.M., Sahlender D.A. and Peden A.A. A targeted siRNA screen to identify SNAREs required for constitutive secretion in mammalian cells. 2010 Traffic. 11, 1191-1204.
  • Miller S.E., Sahlender D., Graham S., Hoening S., Robinson M.S. Peden A.A and Owen D.J. The Molecular Basis for the Endocytosis of Small R-SNAREs by the Clathrin Adaptor CALM. 2011 Cell 147, 1118-1131.

Contact information

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

Project Description

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:

PhD Opportunities

Selected publications

Journal articles