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

A cell-based bioluminescence assay reveals dose-dependent and contextual repression of AP-1-driven gene expression by BACH2.
Vardaka P, Lozano T, Bot C, Ellery J, Whiteside SK, Imianowski CJ, Farrow S, Walker S, Okkenhaug H, Yang J, Okkenhaug K, Kuo P, Roychoudhuri R

Whereas effector CD4 and CD8 T cells promote immune activation and can drive clearance of infections and cancer, CD4 regulatory T (T) cells suppress their function, contributing to both immune homeostasis and cancer immunosuppression. The transcription factor BACH2 functions as a pervasive regulator of T cell differentiation, promoting development of CD4 T cells and suppressing the effector functions of multiple effector T cell (T) lineages. Here, we report the development of a stable cell-based bioluminescence assay of the transcription factor activity of BACH2. Tetracycline-inducible BACH2 expression resulted in suppression of phorbol 12-myristate 13-acetate (PMA)/ionomycin-driven activation of a luciferase reporter containing BACH2/AP-1 target sequences from the mouse Ifng + 18k enhancer. BACH2 expression repressed the luciferase signal in a dose-dependent manner but this activity was abolished at high levels of AP-1 signalling, suggesting contextual regulation of AP-1 driven gene expression by BACH2. Finally, using the reporter assay developed, we find that the histone deacetylase 3 (HDAC3)-selective inhibitor, RGFP966, inhibits BACH2-mediated repression of signal-driven luciferase expression. In addition to enabling mechanistic studies, this cell-based reporter may enable identification of small molecule agonists or antagonists of BACH2 function for drug development.

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Scientific reports, 10, 1, 03 Nov 2020

PMID: 33144667

Selective Autophagy of Mitochondria on a Ubiquitin-Endoplasmic-Reticulum Platform.
Zachari M, Gudmundsson SR, Li Z, Manifava M, Cugliandolo F, 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

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Developmental cell, 55, 2, 26 Oct 2020

PMID: 33108756

ATG13 dynamics in nonselective autophagy and mitophagy: insights from live imaging studies and mathematical modeling.
Dalle Pezze P, Karanasios E, Kandia V, Manifava M, Walker SA, Gambardella Le Novère N, Ktistakis NT

During macroautophagy/autophagy, the ULK complex nucleates autophagic precursors, which give rise to autophagosomes. We analyzed, by live imaging and mathematical modeling, the translocation of ATG13 (part of the ULK complex) to the autophagic puncta in starvation-induced autophagy and ivermectin-induced mitophagy. In nonselective autophagy, the intensity and duration of ATG13 translocation approximated a normal distribution, whereas wortmannin reduced this effect and shifted to a log-normal distribution. During mitophagy, multiple translocations of ATG13 with increasing time between peaks were observed. We hypothesized that these multiple translocations arise because the engulfment of mitochondrial fragments required successive nucleation of phagophores on the same target, and a mathematical model based on this idea reproduced the oscillatory behavior. Significantly, model and experimental data were also in agreement that the number of ATG13 translocations is directly proportional to the diameter of the targeted mitochondrial fragments. Thus, our data provide novel insights into the early dynamics of selective and nonselective autophagy. ATG: autophagy related 13; CFP: cyan fluorescent protein; dsRED: red fluorescent protein; GABARAP: GABA type A receptor-associated protein; GFP: green fluorescent protein; IVM: ivermectin; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MTORC1: mechanistic target of rapamycin kinase complex 1; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PtdIns3P: PtdIns-3-phosphate; ULK: unc-51 like autophagy activating kinase.

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Autophagy, 1, 1, 22 Apr 2020

DOI: 10.1080/15548627.2020.1749401

PMID: 32320309