Faculty of Medicine University of Maribor

 

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Title Development of microphysiological system of small intestine mucosa to investigate effects of microbiota on transepithelial transport and host immune response
Reference number J3-50098
Head dr. Aleksander Mahnič
Collaborative organisations National Laboratory of Health, Environment and Food (NLZOH)

 

Project description

SIBO is a medical condition characterised by an overgrowth of bacteria in the small intestine. The main objective of the project is to develop an experimental platform for in vitro studies of the influence of individual bacteria on trans-epithelial transport in the small intestine. The in vitro model of the small intestinal mucosa will combine advanced 3D bioprinting approaches with microphysiological systems (MPS). This integration will allow the fabrication of bio-structures with well-defined composition and geometrical properties, and a high degree of control over the culture conditions to mimic the natural physiological environment and steer tissue development in the desired direction. The advantages of the proposed experimental platform over existing in vitro models stem from the specific integration of the 3D bioprinted scaffold and the MPS design, which will align the intestinal epithelium and underlying vascularised tissue within a clear optical pathway. Consequently, this will allow continuous imaging and monitoring of molecular transport from the simulated intestinal lumen through the epithelium and into the vasculature. The project will focus on the transport of metabolites from the luminal to the vascular side of an in vitro epithelium integrated into a microphysiological system (MPS). This model will be exposed to metabolites and cellular material from bacterial species known to cause SIBO. We will compare the profiles of the compounds transferring across the epithelium using untargeted metabolomics based on mass spectrometry. The aim is to identify species-specific indicators with high predictive value for the bacterial pathogen causing SIBO.

Figure 1: General description of the components fulfilling the main objective of the project. In vitro SIM (small intestine mucosa) produced within the MPS using 3D bioprinting and grown under continuous monitoring and close environmental control to study the transport of substances of bacterial origin from the luminal to the vascular circuit.


About us

The Department of Microbiology at the Faculty of Medicine of the University of Maribor was established in 2005 and has since then been headed by prof. dr. Maja Rupnik. The team is active in both teaching and research, while no diagnostic activities are performed. The department is strongly linked with the Centre for Medical Microbiology at the National Laboratory of Health, Environment and Food (NLZOH), especially with the Department for Microbiological Research.

The research work is carried out in two major research strands: Clostridioides (Clostridium) difficile and microbiota studies associated with host and the environment. All our research activities ultimately converge to collectively address the One Health approach to microbiome studies. Other involvements of the department are wide-ranging and include authorships in book chapters, original and review scientific publications, peer-reviewed articles, and editorships of national books on the popularisation of science. Our publications can be found in top journals in the field such as the New England Journal of Medicine, Lancet, Lancet Infectious Diseases, Clinical Microbiology and Infection and Nature Reviews Microbiology.

Our team

Head of the department
Dr. Maja Rupnik

Team
Dr. Sandra Janežič
Dr. Valerija Tkalec
Dr. Aleksander Mahnič
Dr. Nejc Stopnišek
Tanja Vrabič
Sabina Mlakar
Tanja Žlender

Other collaborators. dr. Andrej Golle, M.D., Andrej Kraševac Glaser, M.D., Urška Kramar, M.D. and Barbara Janžič, M.D..

Courses offered at the Department

  • Microbiology with immunology in the general medicine programme
  • Microbiology, immunology, and oral microbiology in the dental medicine programme
  • Human microbiota in the postgraduate course Biomedical technology
  • Microbial Pathogenesis in the postgraduate diploma in Biomedical technology

Ongoing projects

Research assignments for students

Student involvement is an important aspect of our research work. To date, the following research work has been completed:
  • Tilen Seničar, Andraž Kukovičič; 2021. Gluten-degrading intestinal bacteria (supervisor, prof. dr. Maja Rupnik, co-supervisor, dr. Jernej Dolinšek, M.D.), 2021; recipients of the Dean's award, the Krka award and the Perlach award, published in Microorganisms, 2021;
  • Ines Blaževič. Work in 2014; co-author of Possible contribution of shoes to Clostridioides difficile transmission within hospitals, Clinical microbiology and infection, 2021 (supervisor, dr. Maja Rupnik);
  • Špela Pintar. Isolation and characterisation of Clostridium difficile in hospitalised patients with chronic inflammatory bowel disease, 2017 (supervisor, dr. Maja Rupnik, co- supervisor, prof. dr. Pavel Skok, M.D.); Dean's award; published in Frontiers in Microbiology 2022;
  • Matija Primec. Molecular and phenotypic characterisation of staphylococci isolated from chronic wounds, 2019 (supervisor, dr. Maja Rupnik, co- supervisor, Vesna Breznik, M.D.); Dean's award.

We also annually host students from international exchanges organised by the International Federation of Medical Student's Associations (IFMSA).

Completed PhDs

  • Dr. Božena Kotnik Kevorkijan. Epidemiological and microbiological approaches for HAI surveillance at the University clinical center Maribor, 2019.
  • Dr. Sabina Horvat. Interactions between various strains of Clostridium difficile and gut microbiota: PhD thesis, 2019.
  • Dr. Andrej Golle. Molecular characterisation of carbapenem-resistant Pseudomonas aeruginosa isolated from patients and the environment, 2019.
  • Dr. Jure Škraban. Interactions of Clostridium difficile with gut microbiota: PhD thesis, 2013.

Organisation of congresses and workshops

The following events have been organised within the Faculty of Medicine of the University of Ljubljana:

  • 2nd International Clostridium difficile Symposium (ICDS), 6-9 June 2007, Maribor;
  • Workshop 'Clostridium difficile - from culture to molecular methods', 3-5 September 2007;
  • Symposium 'Importance, frequency and control of Clostridium difficile infections', 18.4.2013, Brdo pri Kranju;
  • ESCMID Postgraduate Technical Workshops (PGTW) 'Clostridium difficile: Practical aspects of typing and comparative genomics', 2-4 September 2015; collaboration with AGES, Vienna, Austria;
  • 5th Congress of the Slovenian Microbiological Society with international participation, 12-15 October 2015, Maribor;
  • 2nd Slovenian Microbiome Network Symposium 2023, 30 November - 1 December 2023.

Between May 22 - May 27, 2022, the Intensive Program for undergraduate medical students took place at the Faculty of Medicine University of Maribor. The program entitled Diagnostics in gynecology was conducted under the guidance of assist. prof. Jure Knez, PhD. A six-day active learning program comprised 28 students from 5 European faculties. The purpose of the program was to enable students to improve their clinical diagnostic skills in the field of gynecology through innovative teaching methods.

During the workshop, students practice procedures using laparoscopic simulators and an ultrasound examination simulator

Figure 1: Glimpses of work on simulators of laparoscopy and ultrasound examinations (photo: M. Sobočan)

Students at lectures in the field of gynecology, lectures were given by university teachers from Belgrade, Rijeka, Split and Maribor

Figure 2: After completing the work in small groups, the students gained theoretical knowledge through interactive lectures (photo: M. Sobočan)

Group photo of students who participated in workshops in the field of diagnostics in gynecology

Figure 3: Group photo of students and lecturers on day 4 of the intensive program Diagnostics in Gynecology (photo: S. Kos)