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

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, Walker S, Niewczas I, Zoncu R, Clark J, Ktistakis NT

Amino acids are essential activators of mTORC1 via a complex containing RAG GTPases, RAGULATOR and the vacuolar ATPase. Sensing of amino acids causes translocation of mTORC1 to lysosomes, an obligate step for activation. To examine the spatial and temporal dynamics of this translocation, we used live imaging of the mTORC1 component RAPTOR and a cell permeant fluorescent analogue of di-leucine methyl ester. Translocation to lysosomes is a transient event, occurring within 2 min of aa addition and peaking within 5 min. It is temporally coupled with fluorescent leucine appearance in lysosomes and is sustained in comparison to aa stimulation. Sestrin2 and the vacuolar ATPase are negative and positive regulators of mTORC1 activity in our experimental system. Of note, phosphorylation of canonical mTORC1 targets is delayed compared to lysosomal translocation suggesting a dynamic and transient passage of mTORC1 from the lysosomal surface before targetting its substrates elsewhere.

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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, Manifava M, Hummel E, Zimmermann H, Ahmed Q, Domart MC, Collinson L, Ktistakis NT

Autophagosome formation requires sequential translocation of autophagy-specific proteins to membranes enriched in PI3P and connected to the ER. Preceding this, the earliest autophagy-specific structure forming de novo is a small punctum of the ULK1 complex. The provenance of this structure and its mode of formation are unknown. We show that the ULK1 structure emerges from regions, where ATG9 vesicles align with the ER and its formation requires ER exit and coatomer function. Super-resolution microscopy reveals that the ULK1 compartment consists of regularly assembled punctate elements that cluster in progressively larger spherical structures and associates uniquely with the early autophagy machinery. Correlative electron microscopy after live imaging shows tubulovesicular membranes present at the locus of this structure. We propose that the nucleation of autophagosomes occurs in regions, where the ULK1 complex coalesces with ER and the ATG9 compartment.

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Nature communications, 7, 2041-1723, 12420, 2016

PMID: 27510922

01223 496618

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Facility Members

Latest Publications

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

Live cell imaging of early autophagy events: omegasomes and beyond.

E Karanasios, E Stapleton, SA Walker

Journal of visualized experiments : JoVE
77: (2013)

DOI: 10.3791/50484

PMID: 23929131

Characteristics and requirements of basal autophagy in HEK 293 cells.

Musiwaro P, Smith M, Manifava M

Autophagy
9 1554-8635:1407-17 (2013)

PMID: 23800949