Join us for this latest instalment of the 2021 Almroth Wright lecture series with Professor Gad Frankel.
Please register in advance if you would like to attend. This event will be hosted via Microsoft Teams; once you have registered, you will receive a calendar invitation and link via email.
For more information about the Almroth Wright lecture series, please visit our website.
Abstract
Many Gram-negative pathogens use conserved macromolecular nano-syringes to inject bacterial proteins, known as type III secretion system effectors, into eukaryotic cells. While the structure and function of the syringes are conserved (thus refer to as the hardware of pathogenesis), the effectors are pathogen-specific, executing their distinct infection strategies (e.g. intra- or extra-cellular lifestyle). By binding or modifying specific cellular proteins the effectors highjack specific cellular processes and take control of cell signalling (thus referred to as the software of pathogenesis). While for decades studies have focused on each effector at a time, we have recently shown, using the mouse pathogen Citrobacter rodentium as a model organism relying on effectors, that, in fact, the effectors form robust intracellular networks that while hacking wiring of the host’s cell signalling (e.g. innate immune responses) could sustain significant perturbations. Infection with C. rodentium expressing synthetic effector networks triggered vastly different immune responses that unexpectedly were able to clear the infection and induce protective immunity, showing that the robustness of the effector network is mirrored by flexible and adaptable immune responses in the infected host. Using in vivo data generated from infections with >100 disrupted effector networks to train an AI model enabled us to correctly predict infection outcomes of specifically perturbed C. rodentium networks. These results could have important implications for vaccine design and the development of non-antibiotic therapies.
Science 12 Mar 2021: https://doi.org/10.1126/science.abc9531
About the speaker
During my PhD I used the picornavirus Theiler’s Murine Encephalomyelitis Virus as a model to study MS; I received my PhD in Genetics from the Hebrew University of Jerusalem in 1988. After my PhD training, I moved to Stanford University for my postdoc where I started to work on bacterial infections (E. coli and Salmonella). From there I have moved for a short period of time to the Weizmann Institute in Israel, before moving to Imperial College as a Research Fellow in Gordon Dougan’s lab. In 1998 I was appointed Lecturer at Imperial College and was promoted to Reader in 2000 and to Professor in 2002. Between 2011-2015 I held an Honorary Faculty position at the Wellcome Trust Sanger Institute.
I supervised 32 PhD students to graduation; 8 PhD students are currently in training and 2 PhD students will start in October 2021. I hold an MRC programme grant, a Wellcome Investigator Award and a Royal Society International Collaboration Award for Research Professors. I have been granted the 2020 Hamied Foundation UK-India AMR Visiting Professorship. My main industrial partner is GSK Vaccines.