Infection, Immunology & Translational Medicine (IITM) Oxford

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Simon Spiro

Simon Spiro shares his experience of IITM and provides an update on his career.

Simon read for a VetMB in veterinary medicine at Pembroke College, Cambridge between 2004 and 2010, during which time he also undertook an intercalated MA in Pathology in 2006-7. Prior to starting his DPhil, which was supervised by Nicole Zitzmann in Oxford, Simon completed rotations in the labs of Nicole Zitzmann, Jonathan Hodgkin and Sarah Gilbert.

As he explained: “My project focussed on the mechanism of action of iminosugars, a class of broad-spectrum antiviral drugs that work by inhibiting ER quality control pathways, resulting in the production of defective viral proteins. Although these drugs target a cellular pathway, they have very low toxicity against human cells. My project aimed to discern why the viral proteins were so much more susceptible to iminosugars than the cellular proteins.”

Using HIV gp120 as a model, Simon determined that iminosugars cause viral proteins to oxidise and get secreted from the ER more quickly than usual, resulting in subtly different conformations. He added: “However, only a very small proportion of gp120 monomers need to misfold to cause a large drop in viral infectivity, potentially explaining the selectivity paradox. This is hypothesised to be due to amplification effects from gp120 trimerisation and trimer oligomerisation.”

After graduating in 2014, Simon worked as a post-doctoral scientist at the Pirbright Institute, developing vaccines for Marek’s disease. Simon is now a Resident in Anatomic Pathology at the Royal Veterinary College (RVC) as well as a pathology fellow at the Animal and Plant Health Agency (APHA). He told us: “My role is to diagnose and study disease of animals through anatomic pathology techniques including post mortem examinations and histopathology. At the APHA, I am jointly responsible for surveillance of disease within Britain’s livestock as well as contributing pathology expertise to a wide range of research projects on farmed, wild and experimental animals.”

“IITM allowed me to have both the in-depth, concentrated learning experience of a DPhil and the broader education in a range of fields”

Simon told us how IITM benefitted him: “IITM allowed me to have both the in-depth, concentrated learning experience of a DPhil and the broader education in a range of fields through the rotations and associated educational opportunities.”

Talking about his current career Simon said: “Veterinary research can feel isolated from “mainstream” medicine although the overlaps are obvious and important. Veterinary pathology has a key role in human medicine due to the wide use of animal models, as well as expanding the knowledge base of disease processes which may, one day, be important in human pathology. IITM has given me the credibility in human research to be able to work with medical and veterinary researchers on equal footing.”

 “Do what makes you happy”

When asked what advice he would give to current and future IITM students Simon gave a simple answer with a positive message: “Do what makes you happy.”

Publications from IITM

J. L. Miller, S. G. Spiro, S. D. Dowall, I. Taylor, A. Rule, D. S. Alonzi, A. C. Sayce, E. Wright, E. M. Bentley, R. Thom, G. Hall, R. A. Dwek, R. Hewson, and N. Zitzmann, “Minimal In Vivo Efficacy of Iminosugars in a Lethal Ebola Virus Guinea Pig Model,” PLoS ONE, vol. 11, no. 11, p. e0167018, Nov. 2016.

S. Spiro, N. McCaul, R. Derking, D. Alonzi, R. Dwek, R. Sanders, I. Braakman, and N. Zitzmann, “Bypass of Quality Control in Protein Folding Pathways Induces Specific Misfolding of HIV Envelope V2 Loop: Implications for Iminosugars as Antivirals,” AIDS Research and Human Retroviruses, vol. 30, no. 1, pp. A49–A49, Oct. 2014.