Mataleena Parikka wins Tampere University’s 2023 Inventor of the Year Award

The zebrafish (Danio rerio) is a small freshwater fish with distinctive black or blue stripes on a light background. This tropical fish is native to Asia and a popular aquarium fish.

The zebrafish played a role in Mataleena Parikka winning the 2023 Inventor of the Year Award.

Parikka studies the properties of mycobacteria and develops increasingly effective treatments for TB. Mycobacteria, which cause TB, are difficult to kill because they can evade the human immune system and are intrinsically tolerant to antibiotics. This tolerance is partly due to the ability of mycobacteria to form biofilm when they infect the human body. Parikka and her colleagues have been studying mycobacterial biofilms for a decade.

A biofilm is a bacterial colony encased within a self-produced extracellular matrix. Mycobacteria can hide from the human immune system inside this protective matrix. Biofilm formation is not exclusively a mycobacterial ability as many bacteria are capable of producing biofilms.

“The bacterial populations within a colony begin to adapt and diversify to secure their survival in whatever environment they find themselves in. For example, some bacteria can lie dormant for a long time before springing back to life,” Parikka says.

Bacterial adaptation results in the emergence of drug-tolerant subpopulations. Some of these subpopulations often survive antibiotic treatment.

“However, antibiotic tolerance is not the same thing as antibiotic resistance, which is genetic, hereditary and permanent. Tolerance means that bacteria can withstand high doses of antibiotics for a long time, which makes treatment difficult.”

Zebrafish and screening spur progress towards research goals

Parikka leads a research consortium that is looking for ways to prevent the development of drug tolerance in mycobacteria. This is where zebrafish come into the picture.

Parikka and her colleagues use adult zebrafish and the Mycobacterium marinum – which causes a tuberculosis-like infection in zebrafish and is a close relative of the human pathogen – as their research models. Despite the evolutionary distance between zebrafish and humans, fish tuberculosis can be used as a surrogate for modelling human TB.

“Zebrafish is a premier model organism for studying how mycobacteria adapt during infection to develop drug tolerance and how we can disrupt this process,” Parikka says.

In addition to regular fish and bacteria, Parikka’s research group uses fluorescent strains of mycobacteria and zebrafish which allow them to study the progression of TB with unprecedented detail.

A key part of their research is screening for compounds that are known to prevent the formation of bacterial biofilms. Based on this work, the consortium has produced new compounds that have been tested for effectiveness against mycobacterial biofilms with the help of the models developed by the consortium – such as the zebrafish model for TB. The credit for producing the new compounds goes to the partner in the consortium, the University of Helsinki and more specifically Professor Jari Yli-Kauhaluoma and his research group.

“We have carried out a great deal of methodological development to create relevant in-vitro models for screening thousands of new compounds. These screening models have enabled us to discover not only new compounds but also effective candidate compounds, which we have identified by screening a library containing drugs that have been approved for the treatment of other diseases.

Photo: Jonne Renvall

Persistent research and development efforts are also paying off in the number of invention disclosures: Parikka and the research consortium filed four invention disclosures in 2023.

“We disclosed two new drug candidates, the screening method we used to identify the drug candidates, and a method for measuring extracellular DNA, which is one of the main components of the mycobacterial biofilm matrix.”

Collaboration partners are indispensable

The development of new drugs requires collaboration with national and international partners. When the effectiveness and safety of new drugs is evaluated, partners from Australia, Germany and Italy come on board.

The drug candidates identified with the new screening methods developed by Parikka’s research consortium are tested in a Sydney laboratory. The tests are conducted with the help of an aerosol infection model of tuberculosis in mice, meaning that mice are infected with the human TB pathogen via inhalation exposure. A similar infection model cannot be implemented in Finland.

“Although zebrafish serve as a convenient model especially for studying chronic TB infection and biofilms, they alone are not enough to move forward with drug development. As humans are genetically closer to mice than zebrafish, it is important to gain preclinical evidence of the effectiveness of a new drug by testing it with the mouse model,” Parikka notes.

One of the members of Parikka’s consortium is Milka Hammarén, who is leading a study in Heidelberg to develop a high-precision drug carrier. The carrier would enable the concentration and release of TB drugs by targeting the bacterial colony with pinpoint accuracy. This would make treatment more effective and less burdensome for patients. The study is dependent on state-of-the-art technologies and would have been difficult to carry out in Finland from start to finish.

The collaboration partners based in Florence help with a similar challenge but from a different perspective. They study carbonic anhydrase inhibitors. Carbonic anhydrases are enzymes that catalyse a biochemical reaction that is essential to all living things. Blocking the activity of these enzymes opens the door to the development of targeted drugs which, unlike antibiotics, do not disrupt the internal balance of the body. This part of the study is headed by Seppo Parkkila, a professor of anatomy at Tampere University.

The joy of understanding an interesting phenomenon

The current treatment regimen for TB takes a minimum of six months and involves a combination of at least four different antibiotics. The multi-drug regimen takes a toll on the body and has many side effects. As mycobacteria may still be found lurking in the body even after this antibiotic onslaught, there is a clear need for shorter and more effective TB treatment.

Even though Parikka is working to improve TB treatment outcomes, she identifies more as a basic researcher than an inventor.

“I am so curious and fascinated to learn more about the mechanisms of infection biology. It is gratifying to be able to carry out research that sheds light on these mechanisms. But I am also an idealist. What makes my work meaningful is the chance to alleviate suffering around the world.”

Mataleena Parikka is trying to make the world a better place both literally and figuratively: Parikka and her research consortium are strongly committed to non-profit drug development.

“This commitment does not rule out patenting as an important part of the process. We can move forward with drug development even though we are working for non-commercial purposes.”