Dr Andrew Peden

School of Biosciences

Senior Lecturer

a.peden@sheffield.ac.uk
+44 114 222 2312

Full contact details

Dr Andrew Peden
School of Biosciences
D06, Florey Building
Firth Court
Western Bank
Sheffield
S10 2TN
Profile
  • 2019-present: Senior Lecturer, department of Biomedical Science, the University of Sheffield.
  • 2012-2018: Lecturer, department of Biomedical Science, the University of Sheffield
  • 2006-2012: 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.

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:

1) To elucidate the role of SNAREs in constitutive secretion

SNAREs are a familyof 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.

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.

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.

Publications

Show: Featured publications All publications

Journal articles

All publications

Journal articles

Chapters

  • Peden AA (2018) AP-3, Encyclopedia of Signaling Molecules (pp. 333-341). Springer International Publishing RIS download Bibtex download

Conference proceedings papers

  • Serra-Marques A, Grigoriev I, Gordon DE, Peden AA & Akhmanova A (2011) Mechanisms Controlling the Motility and Fusion of Rab6-positive Exocytotic Carriers. MOLECULAR BIOLOGY OF THE CELL, Vol. 22 RIS download Bibtex download
  • Klumperman J, Sachse M, Peden A, Urbe S, Oorschot V, Strous GJ & Scheller RH (2002) The endosome equilibrium: Pathways to and from early endosomes. MOLECULAR BIOLOGY OF THE CELL, Vol. 13 (pp 284A-284A) RIS download Bibtex download
Research group

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)

PhD studentship opportunities

We advertise PhD opportunities (Funded or Self-Funded) on FindAPhD.com

Grants
  • BBSRC
  • MRC
  • Medimmune
  • UCB
Teaching activities

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

Undergraduate:

  • BMS243 Practical Sessions
  • Level 3 Practical and Dissertation Modules
Professional activities
  • Fellow of the Higher Education Academy (FHEA)
  • Editor for BMC Cell biology
  • Reviewer for BBSRC and MRC