Professor Andrew Peden
School of Biosciences
Professor
a.peden@sheffield.ac.uk
+44 114 222 2312
+44 114 222 2312
D06, Florey Building, Florey Building
Full contact details
Professor Andrew Peden
School of Biosciences
D06, Florey Building
Florey Building
Western Bank
Sheffield
S10 2TN
School of Biosciences
D06, Florey Building
Florey Building
Western Bank
Sheffield
S10 2TN
- Profile
-
- 2023-present: Professor, School of Bioscience, the University of Sheffield.
- 2012-2018: Lecturer, Department of Biomedical Science, the University of Sheffield.
- 2019-present: Senior Lecturer, School of Biosciences, the University of Sheffield.
- 2012-2018: Lecturer, Department of Biomedical Science, the University of Sheffield
- 2006-2012: Principal Investigator, University of Cambridge (MRC CDA).
- 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
Featured publications
Journal articles
- S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi. eLife. View this article in WRRO
- Sec22b is a critical and nonredundant regulator of plasma cell maintenance. Proceedings of the National Academy of Sciences, 120(2).
- Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections. Communications Biology, 5.
- Organelle tethering, pore formation and SNARE compensation in the late endocytic pathway. Journal of Cell Science, 134(10).
- Quantitative Flow Cytometry-Based Assays for Measuring Constitutive Secretion, 115-129.
- Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science, 370(6521), ---.
- S-acylation regulates the trafficking and stability of the unconventional Q-SNARE STX19. Journal of Cell Science, 131(20). View this article in WRRO
- 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
- A cell line for detection of botulinum neurotoxin type B. Frontiers in Pharmacology, 8, 796-796. View this article in WRRO
- 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
- 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
- The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells. Cell Reports, 14(11), 2624-2636. View this article in WRRO
- 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
- The N-Ethylmaleimide-Sensitive Factor and Dysbindin Interact To Modulate Synaptic Plasticity. Journal of Neuroscience, 35(19), 7643-7653.
- 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
- Chemical-genetic disruption of clathrin function spares adaptor complex 3-dependent endosome vesicle biogenesis. Molecular Biology of the Cell, 24(15), 2378-2388. View this article in WRRO
- Rab40b regulates trafficking of MMP2 and MMP9 during invadopodia formation and invasion of breast cancer cells. Journal of Cell Science, 126(20), 4647-4658.
- Structural Basis of the Intracellular Sorting of the SNARE VAMP7 by the AP3 Adaptor Complex. Developmental Cell, 22(5), 979-988.
- The molecular basis for the endocytosis of small R-SNAREs by the clathrin adaptor CALM. Cell, 147(5), 1118-1131.
- A targeted siRNA screen to identify SNAREs required for constitutive secretion in mammalian cells. Traffic, 11(9), 1191-1204.
- A genome-wide RNA interference screen identifies two novel components of the metazoan secretory pathway. EMBO Journal, 29(2), 304-314.
- Coiled-coil interactions are required for post-Golgi R-SNARE trafficking. EMBO Reports, 10(8), 851-856.
Preprints
- Plasma cell maintenance and antibody secretion are under the control of Sec22b-mediated regulation of organelle dynamics, Cold Spring Harbor Laboratory.
- A high content microscopy-based platform for detecting antibodies to the nucleocapsid, spike and membrane proteins of SARS-CoV-2, Cold Spring Harbor Laboratory.
All publications
Journal articles
- S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi. eLife. View this article in WRRO
- Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release. EMBO reports. View this article in WRRO
- Establishing SARS-CoV-2 Membrane protein-specific antibodies as a valuable serological target via high-content microscopy. iScience, 107056-107056.
- Sec22b is a critical and nonredundant regulator of plasma cell maintenance. Proceedings of the National Academy of Sciences, 120(2).
- Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication. Life Science Alliance, 6(1), e202201449-e202201449.
- Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections. Communications Biology, 5.
- Acat1/Soat1 knockout extends the mutant Npc1 mouse lifespan and ameliorates functional deficiencies in multiple organelles of mutant cells.. Proc Natl Acad Sci U S A, 119(18), e2201646119.
- ALG-2 and peflin regulate COPII targeting and secretion in response to calcium signaling. Journal of Biological Chemistry, 297(6). View this article in WRRO
- Author Correction: Vps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin-dependent functions.. Nat Commun, 12(1), 5828.
- An open-source framework for automated high-throughput cell biology experiments. Frontiers in Cell and Developmental Biology, 9.
- Organelle tethering, pore formation and SNARE compensation in the late endocytic pathway. Journal of Cell Science, 134(10).
- Identification of additional outer segment targeting signals in zebrafish rod opsin.. J Cell Sci.
- Quantitative Flow Cytometry-Based Assays for Measuring Constitutive Secretion, 115-129.
- Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science, 370(6521), ---.
- A platform for context-specific genetic engineering of recombinant protein production by CHO cells. Journal of Biotechnology, 312, 11-22.
- 2601. Identification of Staphylococcus aureus Genetic Factors Associatiated with the Subversion of Macrophage Phagosomal Acidification. Open Forum Infectious Diseases, 6(Supplement_2), S904-S904.
- The C7orf43/TRAPPC14 component links the TRAPPII complex to Rabin8 for preciliary vesicle tethering at the mother centriole during ciliogenesis. Journal of Biological Chemistry, 294(42), 15418-15434.
- BoNT/X: A tool to study intracellular trafficking and membrane fusion. Toxicon, 156, S90-S90.
- An enzymatic reporter cell line for detection of botulinum neurotoxin type B. Toxicon, 156, S25-S25.
- S-acylation regulates the trafficking and stability of the unconventional Q-SNARE STX19. Journal of Cell Science, 131(20). View this article in WRRO
- 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
- A cell line for detection of botulinum neurotoxin type B. Frontiers in Pharmacology, 8, 796-796. View this article in WRRO
- 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
- 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
- The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells. Cell Reports, 14(11), 2624-2636. View this article in WRRO
- 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
- The N-Ethylmaleimide-Sensitive Factor and Dysbindin Interact To Modulate Synaptic Plasticity. Journal of Neuroscience, 35(19), 7643-7653.
- 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
- Chemical-genetic disruption of clathrin function spares adaptor complex 3-dependent endosome vesicle biogenesis. Molecular Biology of the Cell, 24(15), 2378-2388. View this article in WRRO
- Uncoupling the Functions of CALM in VAMP Sorting and Clathrin-Coated Pit Formation. PLoS ONE, 8(5). View this article in WRRO
- Abstract B4: Tumor-educated CD11c+/CD11bint/Gr-1- regulatory dendritic cells show a mutated pattern of trafficking molecules implicated in cytokine secretion.. Checkpoint Pathways Regulating Immune Responses.
- Rab40b regulates trafficking of MMP2 and MMP9 during invadopodia formation and invasion of breast cancer cells. Journal of Cell Science, 126(20), 4647-4658.
- Distinct and overlapping roles for AP-1 and GGAs revealed by the "knocksideways" system. Current Biology, 22(18), 1711-1716.
- Structural Basis of the Intracellular Sorting of the SNARE VAMP7 by the AP3 Adaptor Complex. Developmental Cell, 22(5), 979-988.
- The molecular basis for the endocytosis of small R-SNAREs by the clathrin adaptor CALM. Cell, 147(5), 1118-1131.
- Autophagic substrate clearance requires activity of the syntaxin-5 SNARE complex. Journal of Cell Science, 124(3), 469-482.
- Myosin VI and its binding partner optineurin are involved in secretory vesicle fusion at the plasma membrane. Molecular Biology of the Cell, 22(1), 54-65. View this article in WRRO
- α-Synuclein impairs macroautophagy: implications for Parkinson's disease. The Journal of Experimental Medicine, 207(10), i29-i29.
- α-Synuclein impairs macroautophagy: Implications for Parkinson's disease. Journal of Cell Biology, 190(6), 1023-1037. View this article in WRRO
- FIP1/RCP binding to Golgin-97 regulates retrograde transport from recycling endosomes to the trans-Golgi network. Molecular Biology of the Cell, 21(17), 3041-3053. View this article in WRRO
- A targeted siRNA screen to identify SNAREs required for constitutive secretion in mammalian cells. Traffic, 11(9), 1191-1204.
- Ricin toxin hits a retrograde roadblock. Cell, 141(2), 222-224.
- A genome-wide RNA interference screen identifies two novel components of the metazoan secretory pathway. EMBO Journal, 29(2), 304-314.
- Mistargeting of SH3TC2 away from the recycling endosome causes Charcot-Marie-Tooth disease type 4C. Human Molecular Genetics, 19(6), 1009-1018.
- Evolution of specificity in the eukaryotic endomembrane system. International Journal of Biochemistry and Cell Biology, 41(2), 330-340.
- Hermansky-pudlak syndrome protein complexes associate with phosphatidylinositol 4-kinase type II α in neuronal and non-neuronal cells. Journal of Biological Chemistry, 284(3), 1790-1802.
- Coiled-coil interactions are required for post-Golgi R-SNARE trafficking. EMBO Reports, 10(8), 851-856.
- Transport of LDL-derived cholesterol from the NPC1 compartment to the ER involves the trans-Golgi network and the SNARE protein complex (Proceedings of the National Academy of Sciences of the United States of America (2008) 105, 43, (16513-16518) DOI:10.1073/pnas.0807450105). Proceedings of the National Academy of Sciences of the United States of America, 105(49), 19561.
- Transport of LDL-derived cholesterol from the NPC1 compartment to the ER involves the trans-Golgi network and the SNARE protein complex. Proceedings of the National Academy of Sciences of the United States of America, 105(43), 16513-16518.
- Sdmg1 is a conserved transmembrane protein associated with germ cell sex determination and germline-soma interactions in mice. Development, 135(8), 1415-1425.
- Erratum: Death-receptor activation halts clathrin-dependent endocytosis (Proceedings of the National Academy of Sciences of the United States of America (July 5, 2006) 103, 27 (10283-10288) DOI:10.1073/pnas.0604044103). Proceedings of the National Academy of Sciences of the United States of America, 103(36), 13560.
- BLOC-1 complex deficiency alters the targeting of adaptor protein complex-3 cargoes. Molecular Biology of the Cell, 17(9), 4014-4026.
- Death-receptor activation halts clathrin-dependent endocytosis. Proceedings of the National Academy of Sciences of the United States of America, 103(27), 10283-10288.
- Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes. Molecular Biology of the Cell, 16(11), 5356-5372.
- Molecular recognition by a binary code. Journal of Molecular Biology, 348(5), 1153-1162.
- The FIP3-Rab11 protein complex regulates recycling endosome targeting to the cleavage furrow during late cytokinesis. Molecular Biology of the Cell, 16(2), 849-860.
- Class I FIPs, Rab11-binding proteins that regulate endocytic sorting and recycling. Methods in Enzymology, 403, 512-525.
- The endo-lysosomal sorting machinery interacts with the intermediate filament cytoskeleton. Molecular Biology of the Cell, 15(12), 5369-5382.
- Molecular characterization of Rab11 interactions with members of the family of Rab11-interacting proteins. Journal of Biological Chemistry, 279(32), 33430-33437.
- The RCP-Rab11 complex regulates endocytic protein sorting. Molecular Biology of the Cell, 15(8), 3530-3541.
- AP-3-dependent mechanisms control the targeting of a chloride channel (ClC-3) in neuronal and non-neuronal cells.. J Biol Chem, 279(24), 25430-25439.
- Rab14 Is Involved in Membrane Trafficking between the Golgi Complex and Endosomes. Molecular Biology of the Cell, 15(5), 2218-2229.
- Localization of the AP-3 adaptor complex defines a novel endosomal exit site for lysosomal membrane proteins. Journal of Cell Biology, 164(7), 1065-1076. View this article in WRRO
- Genetic and phenotypic analysis of the mouse mutant mh2J, an Ap3d allele caused by IAP element insertion. Mammalian Genome, 14(3), 157-167.
- Assembly and function of AP-3 complexes in cells expressing mutant subunits. Journal of Cell Biology, 156(2), 327-336. View this article in WRRO
- The Di-leucine Motif of Vesicle-associated Membrane Protein 4 Is Required for Its Localization and AP-1 Binding. Journal of Biological Chemistry, 276(52), 49183-49187.
- A genomic perspective on membrane compartment organization. Nature, 409(6822), 839-841.
- Abnormal expression and subcellular distribution of subunit proteins of the AP-3 adaptor complex lead to platelet storage pool deficiency in the pearl mouse. Blood, 94(1), 146-155.
- The β3A subunit gene (Ap3b1) of the AP-3 adaptor complex is altered in the mouse hypopigmentation mutant pearl, a model for Hermansky-Pudlak syndrome and night blindness. Human Molecular Genetics, 8(2), 323-330.
- Mutation in AP-3 δ in the mocha mouse links endosomal transport to storage deficiency in platelets, melanosomes, and synaptic vesicles. Neuron, 21(1), 111-122.
- Characterization of the adaptor-related protein complex, AP-3. Journal of Cell Biology, 137(4), 835-845. View this article in WRRO
- A sensitive cell-based assay for testing potency of Botulinum neurotoxin type A. ALTEX.
- Oxidized cholesteryl ester induces exocytosis of dysfunctional lysosomes in lipidotic macrophages. Traffic.
Chapters
- AP-3, Encyclopedia of Signaling Molecules (pp. 333-341). Springer International Publishing
Conference proceedings papers
- Sec22b is indispensable for plasma cell maintenance and antibody secretion. EUROPEAN JOURNAL OF IMMUNOLOGY, Vol. 51 (pp 9-9)
- Mechanisms Controlling the Motility and Fusion of Rab6-positive Exocytotic Carriers. MOLECULAR BIOLOGY OF THE CELL, Vol. 22
- The endosome equilibrium: Pathways to and from early endosomes. MOLECULAR BIOLOGY OF THE CELL, Vol. 13 (pp 284A-284A)
Preprints
- S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi, eLife Sciences Publications, Ltd.
- S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi, eLife Sciences Publications, Ltd.
- S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi, eLife Sciences Publications, Ltd.
- S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi, Cold Spring Harbor Laboratory.
- Plasma cell maintenance and antibody secretion are under the control of Sec22b-mediated regulation of organelle dynamics, Cold Spring Harbor Laboratory.
- A high content microscopy-based platform for detecting antibodies to the nucleocapsid, spike and membrane proteins of SARS-CoV-2, Cold Spring Harbor Laboratory.
- SARS-CoV-2 spike downregulates tetherin to enhance viral spread, Cold Spring Harbor Laboratory.
- Cholesteryl Hemiazelate Induces Lysosome Dysfunction and Exocytosis in Macrophages, Cold Spring Harbor Laboratory.
- Acat1gene KO restores TGN cholesterol deficiency in mutant NPC1 cells and expands mutantNpc1mouse lifespan, Cold Spring Harbor Laboratory.
- ALG-2 and Peflin Stimulate or Inffibit Copii Targeting and Secretion in Response to Calcium Signaling, Cold Spring Harbor Laboratory.
- Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication, Cold Spring Harbor Laboratory.
- S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi. eLife. View this article in WRRO
- Research group
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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
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- BBSRC
- MRC
- Medimmune
- UCB
- Teaching activities
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- BIS213: Skills in Biomedical Science (Herceptin practical co-ordinator).
- BIS225: Molecular and Cell Biology.
- BMS376: Membrane Dynamics in Health and Disease.
- Supervise level 3 research projects.
- Supervise level 4 and masters research projects.
- Professional activities and memberships
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- 2023-present BBSRC Committee D Core Member
- 2021-present Member of the WHO COVID-19 assays group
- 2018-present Carnegie Trust research assessor