Life Sciences Research for Lifelong Health

Simon Walker

Simon obtained his first degree in Biochemistry at Heriot-Watt University in Edinburgh before moving to the John Innes Centre in Norwich where he studied for his PhD under the supervision of Allan Downie looking at the role of calcium signalling during legume symbiosis.

Simon then went to work as a postdoc for four years in Pete Cullen's lab in the Department of Biochemistry at Bristol University where he investigated the GAP1 family of ras GTPase-activating proteins.

​Having become interested in the application of imaging technologies to answer biological quesions Simon moved to the Babraham Institute in 2004 where he helped establish the core Imaging Facility.

Simon now manages the Facility which has over 100 registered users based within the Institute and an increasing number of commercial users based both on and off campus.

Latest Publications

Autophagosome biogenesis machinery.
Walker SA, Ktistakis NT

We review current knowledge of the process of autophagosome formation with special emphasis on the very early steps: turning on the autophagy pathway, assembling the autophagy machinery, and building the autophagosome. The pathway is remarkably well co-ordinated spatially and temporally, and it shows broad conservation across species and cell types, including neurons. In addition, although much current knowledge derives mostly from settings of non-selective autophagy, recent work also indicates that selective autophagy, and more specifically mitophagy, shows similar dynamics. Having an understanding of this remarkable process may help the design of novel therapeutics for neurodegeneration and other pathologies.

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Journal of molecular biology, , 1089-8638, , 2019

PMID: 31705882

Selective Autophagy of Mitochondria on a Ubiquitin-Endoplasmic-Reticulum Platform.
Zachari M, Gudmundsson SR, Li Z, Manifava M, Shah R, Smith M, Stronge J, Karanasios E, Piunti C, Kishi-Itakura C, Vihinen H, Jokitalo E, Guan JL, Buss F, Smith AM, Walker SA, Eskelinen EL, Ktistakis NT

The dynamics and coordination between autophagy machinery and selective receptors during mitophagy are unknown. Also unknown is whether mitophagy depends on pre-existing membranes or is triggered on the surface of damaged mitochondria. Using a ubiquitin-dependent mitophagy inducer, the lactone ivermectin, we have combined genetic and imaging experiments to address these questions. Ubiquitination of mitochondrial fragments is required the earliest, followed by auto-phosphorylation of TBK1. Next, early essential autophagy proteins FIP200 and ATG13 act at different steps, whereas ULK1 and ULK2 are dispensable. Receptors act temporally and mechanistically upstream of ATG13 but downstream of FIP200. The VPS34 complex functions at the omegasome step. ATG13 and optineurin target mitochondria in a discontinuous oscillatory way, suggesting multiple initiation events. Targeted ubiquitinated mitochondria are cradled by endoplasmic reticulum (ER) strands even without functional autophagy machinery and mitophagy adaptors. We propose that damaged mitochondria are ubiquitinated and dynamically encased in ER strands, providing platforms for formation of the mitophagosomes.

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Developmental cell, , 1878-1551, , 2019

PMID: 31353311

RNA proximity sequencing reveals the spatial organization of the transcriptome in the nucleus.
Morf J, Wingett SW, Farabella I, Cairns J, Furlan-Magaril M, Jiménez-García LF, Liu X, Craig FF, Walker S, Segonds-Pichon A, Andrews S, Marti-Renom MA, Fraser P

The global, three-dimensional organization of RNA molecules in the nucleus is difficult to determine using existing methods. Here we introduce Proximity RNA-seq, which identifies colocalization preferences for pairs or groups of nascent and fully transcribed RNAs in the nucleus. Proximity RNA-seq is based on massive-throughput RNA barcoding of subnuclear particles in water-in-oil emulsion droplets, followed by cDNA sequencing. Our results show RNAs of varying tissue-specificity of expression, speed of RNA polymerase elongation and extent of alternative splicing positioned at varying distances from nucleoli. The simultaneous detection of multiple RNAs in proximity to each other distinguishes RNA-dense from sparse compartments. Application of Proximity RNA-seq will facilitate study of the spatial organization of transcripts in the nucleus, including non-coding RNAs, and its functional relevance.

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Nature biotechnology, 37, 1546-1696, 793-802, 2019

PMID: 31267103

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Facility Members

Latest Publications

Autophagosome biogenesis machinery.

Walker SA, Ktistakis NT

Journal of molecular biology
1089-8638: (2019)

PMID: 31705882

Selective Autophagy of Mitochondria on a Ubiquitin-Endoplasmic-Reticulum Platform.

Zachari M, Gudmundsson SR, Li Z

Developmental cell
1878-1551: (2019)

PMID: 31353311

RNA proximity sequencing reveals the spatial organization of the transcriptome in the nucleus.

Morf J, Wingett SW, Farabella I

Nature biotechnology
37 1546-1696:793-802 (2019)

PMID: 31267103

Assembly of early machinery for autophagy induction: novel insights from high resolution microscopy.

Ktistakis NT, Walker SA, Karanasios E

Oncotarget
1949-2553: (2016)

PMID: 27829241

Dynamics of mTORC1 activation in response to amino acids.

Manifava M, Smith M, Rotondo S

eLife
5 2050-084X: (2016)

PMID: 27725083

Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles.

Karanasios E, Walker SA, Okkenhaug H

Nature communications
7 2041-1723:12420 (2016)

PMID: 27510922

Localizing the lipid products of PI3Kγ in neutrophils.

Norton L, Lindsay Y, Deladeriere A

Advances in biological regulation
2212-4934: (2015)

PMID: 26596865

A novel phosphate-starvation response in fission yeast requires the endocytic function of Myosin I.

Petrini E, Baillet V, Cridge J

Journal of cell science
1477-9137: (2015)

PMID: 26345368

Etoposide Induces Nuclear Re-Localisation of AID.

LJ Lambert, S Walker, J Feltham

PloS one
8 12:e82110 (2013)

DOI: 10.1371/journal.pone.0082110

PMID: 24324754

Dynamic association of the ULK1 complex with omegasomes during autophagy induction.

Karanasios E, Stapleton E, Manifava M

Journal of cell science
126 1477-9137:5224-38 (2013)

PMID: 24013547