Microbiom-induced pruritus

o Wider research context / theoretical framework
Chronic pruritus affects a substantial proportion of the population. Therapeutic options, however, are far from
being satisfactory, jeopardizing the quality of life. Thus, there is an unmet medical need for new treatment
strategies. The skin microbiome profoundly influences itch symptoms, which in turn activates sensory
neurons, assumedly also by means of TRP ion channel activation.
o Hypotheses/research questions /objectives
We envision a therapeutic concept encompassing individualized interventions targeting each patient’s itchcausing microorganisms as well as inhibition of the TRP channels involved downstream of the particular
microorganisms. First, we will identify microorganisms that cause itch in a TRP ion channel-dependent
manner. Building on this, we aim to exploit these new mechanisms to provide the basis for personally
tailored drug combinations targeting TRP channels.
o Approach/methods
Our research plan includes state-of-the-art sequencing techniques to identify microorganisms causing itch,
cellular and ex-vivo skin models that allow to explore mechanistic involvement of TRP channels with high
throughput, knockout animals and itch models to corroborate TRP channel involvement in itch in-vivo, and
translational psychophysical experiments with humans.
o Level of originality / innovation
Here, we propose to establish a fundamentally new therapeutic approach, personalized for each individual
patient, applying the principle of precision medicine to patients suffering from itch. The project is highly
interdisciplinary, involving four separate and quite distant academic fields and groups, reaching from the
respective patients and their microbiome to the individual chemical molecules and their molecular targets.
Beyond scientific progress, the proposed approach would constitute a significant step for the post-doctoral
researchers trained in this interdisciplinary project and will thus strengthen the research environment in
Austria.
o Primary researchers involved
Each member of our multidisciplinary research group will provide indispensable scientific and unique
methodological contributions. Dermatologist Georg Stary leads recruitment and in-depth characterization of
patients with the respective dermatological disorders. Michael Fischer’s group performs psychophysical
experiments in healthy volunteers, ex-vivo skin models regarding TRP channels and the design of the clinical
trial fall. The microbiome expert David Berry enables us to characterize the skin microbiome using ampliconbased and shotgun metagenomic sequencing as well as cultivation-based methods. Based on that, Thomas
Böttcher provides elaborated chemical analysis and fractionation for the discovery of the involved molecules.