Wiebke joined the fabulous Spence lab as a postdoc in 2015 and is investigating acquired mechanisms of disease tolerance in malaria using both mouse models and human challenge studies. First she led a project asking whether host control of inflammation was imprinted through innate memory (the epigenetic reprogramming of myeloid progenitors) and developed a Plasmodium chabaudi reinfection mouse model and low input ChIPseq pipeline to test this hypothesis. She did not find evidence of epigenetic modifications, but instead uncovered that monocytes take on tissue-protective functions during reinfection after arriving in the remodelled spleen (doi.org/10.7554/eLife.63838).
Next, Wiebke joined a collaborative team of scientists and clinicians developing a reinfection model of falciparum and vivax malaria (led by Angela Minassian and Simon Draper at the University of Oxford). Malaria-naive adult volunteers were infected three times and their immune response tracked: volunteers infected for the first time triggered indiscriminate cytotoxic T cell activation, leading to tissue damage. Upon reinfection these pathogenic T cells were silenced and volunteers instead mounted a benign stem-like helper T cell response, which protected tissues (doi.org/10.1101/2021.08.19.21262298). Naturally acquired immunity to malaria therefore prioritises host fitness over parasite clearance to rapidly minimise harm caused by the infection.
This exciting new paradigm opens up new avenues for malaria control programmes, which Wiebke is now investigating as Researcher Co-Investigator through an MRC Experimental Medicine Grant. This role recognises her substantial input into the design, grant writing and management of this huge project. She is a member of the steering group for the exciting BIO-004 trial (currently recruiting! trials.ovg.ox.ac.uk/trials/bio-004) in which brave participants will be experimentally infected with malaria three times while drinking heavy water which labels their proliferating immune cells. This will allow her to understand the mechanisms of adaptive T cell reprogramming.
Wiebke is also pushing the boundaries of human tissue immunology and has a soft spot for stromal cells; which were long regarded as little more than inert scaffolding but are actually incredibly important for directing immune responses. Wiebke is working with human bone marrow and has set-up the perfusion of explanted human spleens to characterise the stromal cell response to malaria. This work is a collaboration with Damian Mole (Institute for Regeneration and Repair, CMVM, University of Edinburgh - ISLAND study to obtain human spleens), Pierre Buffet (Institut Pasteur, Paris, France - spleen perfusion guru) and Michalina Mazurczyk (MRC Human Immunology Unit, University of Oxford - imaging mass cytometry expertise).
Wiebke has unpicked the mechanisms of malaria immunology since her EviMalaR PhD in the labs of Jean Langhorne (NIMR, London, UK) and Robert Sauerwein (Radboud UMC Nijmegen, The Netherlands). When she is not in the lab, Wiebke enjoys digging up the garden, drinking whiskey sours and scuba diving in the cold waters of Scotland.