Supervisors:

prof. dr hab. Magdalena Chadzińska (magdalena.chadzinska@uj.edu.pl)
dr Magdalena Widziołek-Pooranachandran

Institute of Zoology and Biomedical Research

Background information:

Most infection-driven diseases are caused by bacteria residing in a complex system referred to as biofilm. This ecosystem is often polymicrobial and reflects complicated interactions amongst bacterial species. Biofilm protects bacteria from the host's immune system and limits the penetration of therapeutics. One example of such biofilm is dental plaque covering teeth surface. It is composed of a range of bacterial species varying from commensals to pathogens. Late colonisers of biofilm cause microbial dysbiosis, which is key to periodontitis. Furthermore, reports indicate a connection between oral diseases and life-threatening diseases such as cardiovascular or neurodegenerative diseases, however mechanisms behind bacteria dissemination are not known. Possibly, microcolonies detach from biofilm and spread via bloodstream. Most studies are performed in simplified in vitro environment and concentrate on the effect of single bacterial infection, however, this does not reflect the nature of complicated polymicrobial interactions with the host cells in an organism, which can differently shape the infection outcomes.

The main question to be addressed in the project:

The aim of this project is to establish a new in vivo model to investigate how bacterial compositions of oral biofilms modulates host immune response, and how it is implicated in vascular damage as a potential mechanism of bacterial dissemination.

Information on the methods/description of work:

In this project, we will use polymicrobial biofilms composed of core oral bacteria species. We will study: (i) phagocyte and biofilm interactions, (ii) effect of bacteria and/or phagocytes on vascular damage, (iii) bacterial composition upon infection of the host, (iv) biomaterials with anti-biofilm properties and immunomodulatory factors to observe their ability to fight infections.

We will use zebrafish larvae (Danio rerio) – well established model, that thanks to larvae transparency and availability of transgenic fish lines with specifically labelled cell types e.g., neutrophils allows real-time microscopic observation of the host-pathogen interactions.

Additional information (e.g Special requirements from the student):

We are seeking a highly motivated PhD student with a MSci in life science (biology, biotechnology or related), preferentially with experience in molecular/microbiological techniques and confocal microscopy, and with good oral and written English. Experience in working with zebrafish will be an advantage.

Successful candidate will have opportunity to work in a stimulating, international environment, in a pioneer team for studying oral pathogens- host interactions using zebrafish model. This will provide the opportunity for exchange and collaborations with scientists from the top World Universities.

Place/name of potential foreign collaborator:

The project will be conducted at the Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland, in collaboration with the University of Sheffield, The University of Glasgow and Queen Mary College, University of London.

References:

[1]Farrugia C et al. Mechanisms of vascular damage by systemic dissemination of the oral pathogen Porphyromonas gingivalis. FEBS J. 2021 Mar;288(5):1479-1495. doi: 10.1111/febs.15486.

[2] Millhouse E, Jose A, Sherry L, Lappin DF, Patel N, Middleton AM, Pratten J, Culshaw S, Ramage G. Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules. BMC Oral Health. 2014 Jun 28;14:80. doi: 10.1186/1472-6831-14-80. PMID: 24972711; PMCID: PMC4080992.