Katrien Forier

Katrien Forier

Contact

Katrien Forier
Biophotonic Imaging Group
Laboratory for General Biochemistry and Physical Pharmacy
Ghent University
Harelbekestraat 72
9000 Gent
Belgium
Tel: 0032 9 2648047 (secretary)
Tel: 0032 9 2648049 (direct)
Fax: 0032 9 2648189
E-mail: katrien.forier@UGent.be

Biography

2009–Present

PhD candidate at the lab of General Biochemistry and Physical Pharmacy of Ghent University.

2012-Present

Teaching Assistant on the subject of Physical Pharmacy (Practical exercises).

Academic years 2010-2011 and 2011-2012

Tutor for the Pharmaceutical Bachelor Test.

2004-2009

Studied Pharmaceutical sciences at the Catholic University of Leuven.  Graduated as Master of Science in Drug Development with the professional  title of pharmacist.
Master thesis subject: Improving the signal to noise ratio of a commercial surface plasmon resonance biosensor using nanoparticle and nanodisc arrays. The master thesis was a joint project between IMEC (Leuven) and the Chalmers University of Technology (Göteborg, Sweden).

Research interests

Biofilms, Cystic fibrosis, Advanced light microscopy methods, Burkholderia cepacia complex, Biophotonics, Drug Delivery, Nanotechnology, Biosensors, Surface Plasmon Resonance.

Summary of Research Project(s)

In my project, I’m trying to develop nanoparticles in such a way that they can be used to improve the treatment efficiency of pulmonary biofilm infections in cystic fibrosis patients. This is a 5-year project crammed into one sentence and I’m aware that it contains a lot of technical terms. Allow me to explain them.

Cystic fibrosis (CF) is a genetic disease which causes the mucus, which is present in the respiratory- , digestive- and reproductive tract, to become thick and sticky. In the lungs, the mucociliary clearance is crucial in keeping the lungs dust and pathogen free. In CF patients, this mechanism is failing and initiates a vicious cycle of infection, inflammation and destruction of lung tissue (Figure 1). This leads to pulmonary failure and early death of the patient. Despite of all the current knowledge on this disease, the average life expectancy of these patients is about 40 years.

Katrien Forier research project1Katrien Forier research project2

One could reason: “Hey, if we get rid of the pathogens, we interrupt this cycle!”. Correct, but not as easy as it seems. The pathogens listed on Figure 1 are quite good at forming biofilms. Biofilms are communities of bacteria that are able to embed themselves in a gel like matrix and are adherent to a surface (Figure 2). This matrix is produced by the biofilm bacteria themselves and allows the bacteria to survive and thrive under extreme conditions. Biofilms are found from boiling hydrothermal vents at the ocean floor to searing deserts, where they can be found as cryptobiotic soils and desert varnish. In fact, the image that people have of bacteria as free swimming single bacterial cells, also known as planktonic bacteria, is not complete. There is a higher percentage of bacteria living as biofilm associated cells than there are planktonic cells.

What is the link with cystic fibrosis? When bacteria colonize the lungs and form biofilms, the bacteria cannot be cleared by the immune system. The biofilm matrix blocks phagocytosis and the action of antibodies. Also, biofilm bacteria show an increased resistance against antibiotics thus biofilms cannot be eradicated using antibiotic therapy. Therefore, the vicious cycle in CF cannot be interrupted using our current state of the art in antimicrobial therapy.

As a novel approach to overcome resistance in biofilms, researchers are now focusing on using nanoparticles for drug delivery. Several scientists have reported a higher killing of biofilm bacteria when using liposome encapsulated antibiotics. This observation is just the first step in developing smart nanoparticles for drug delivery to biofilms. If a nanoparticle is cleverly engineered, it is able to diffuse across the sticky lung mucus, reaches the infection site, enters the biofilm and releases its antimicrobial content in close proximity to the bacteria. These are a whole lot of steps and fundamental insight into the behavior of nanoparticles in mucus and biofilms will be necessarily.

So, what is my contribution in this story? My project aims to improve the fundamental insight into the transport of particles in human CF sputum and Burkholderia multivorans biofilms and to translate this knowledge into a working nanomedicinal formulation. The first part of my project focused on the transport of model nanoparticles in biofilms and CF sputum, since this information is crucial for the development of a nanocarrier that is able to reach the infection site. It seems that PEGylation is the key to mobility of particles in mucus and biofilms. [3] In a second part, the focus was put on the size limit for nanoparticles to have access to denser clusters of bacteria within the biofilm. Particles of 100 nm in diameter access the clusters well while access is more limited for 200 nm particles and almost completely inexistent for 500 nm particles. It can be concluded that nanoparticles for drug delivery to these biofilms are ideally smaller than 200 nm to be able to deliver their antimicrobial payload in close proximity to the bacteria. This is good news, since many commonly used nanoparticles for drug delivery are within this size range. In a third part of my research, the focus will be put on developing a liposomal formulation which is optimized for drug delivery in biofilms according to our previous findings. The transport in human CF sputum and in biofilms, as well as the antimicrobial activity of the formulation will be evaluated. These experiments are still ongoing.

This project was done in collaboration with the Laboratory of Pharmaceutical Microbiology and with Prof. MD. Frans De Baets of the Department of Pediatrics at the University Hospital of Ghent.

References

[1] Braunwald E., Atlas of Internal Medicine, McGraw-Hill, 2007, 3rd ed.
[2] Stoodley P. et al., Ann. Rev. Microbiol. (2002), vol 56, p. 87-209  
[3] Forier K. et al., Nanomedicine (2013), vol 8, issue 6, p. 935-949

Interesting links

A comprehensive movie explaining biofilm formation: http://vimeo.com/30571458
Cystic fibrosis foundation: http://www.cff.org/
Belgische vereniging voor mucoviscidose: http://nl.muco.be/index.php