Over PLN 6 million from the National Science Center for basic research at IIMCB
Dr. Wojciech Pokrzywa, prof. Matthias Bochtler, and doctoral researcher Aleksandra Uryga are among the recipients of grants from the National Science Centre. Their research will focus on pathogenic mutations in cells, the search for treatments for childhood leukemia, and the impact of plant hormones on liver diseases in humans.
Understanding harmful mutations
The study by Dr. Wojciech Pokrzywa is based on the discovery of harmful mutations in key enzymes responsible for labeling and removing defective proteins. “Proper protein degradation is a prerequisite for cell health. Understanding how mutations impair the ability of enzymes to mark proteins for degradation allows us to determine which ones accumulate in the cell, and to study ways to restore their proper balance,” explains Dr. Pokrzywa. Using models of C. elegans that mimic human mutations, as well as advanced imaging and biochemical analysis techniques, his team will study the impact of these defects on protein stability and whole organism function. Their findings could open up therapeutic options for severe multisystem disorders based on new strategies for correcting protein imbalances.
In addition to clarifying the molecular mechanisms behind these disorders, the researchers aim to identify small molecules that reinforce the interaction between the enzyme and its substrates. High-throughput virtual screening and structural modeling will guide the search for compounds capable of counteracting the pathogenic mutations. Ultimately, this work could inspire new strategies to correct disease-related protein imbalances, offering hope for more effective treatments.
The research project Targeting Proteinopathies: Understanding and Mitigating the Effects of Pathogenic Mutations in Cullin-RING Ubiquitin Ligase Receptors has received a four-year OPUS 27 grant (panel NZ3) from the National Science Centre (NCN), worth PLN 2,946,788.
Artificial intelligence will help fight leukemia
Lymphoblastic leukemia (ALL) is the most common childhood cancer, which, without treatment, quickly leads to death. Therapy with bacterial asparaginases, a key treatment for ALL, is often associated with an immune response that reduces the effectiveness of treatment.
“Long-term exposure of to the bacterial asparaginase triggers an overt immune response in 30% of patients, and a silent immune response, that can also render treatment ineffective, in another 20%", stresses Prof. Matthias Bochtler, head of the Laboratory of Structural Biology at IIMCB. The grant-awarded research project envisions designing less immunogenic enzymes, paving the way for personalized cancer therapy.
The study will use machine learning algorithms, the basis of artificial intelligence. “If our approach proves successful, the study will become another example of the application of personalized medicine developed based on a patient's genotype,” Prof. Bochtler says.
Prof. Matthias Bochtler was awarded an OPUS grant under the NZ1 panel for a study entitled “Stealth” asparaginases as improved protein drugs for the treatment of childhood acute lymphoblastic leukemia (ALL). This study will be funded by NCN with PLN 2,875,400.
Does a Plant Hormone Also Affect the Human Liver?
Indole-3-acetic acid (IAA) is a plant hormone and a derivative of tryptophan. Humans do not produce it — its sources are limited to diet and microbial metabolism in the gut. Its effects on human cells, particularly the liver, remain poorly understood. Studies have repeatedly shown that both insufficient and excessive levels of IAA in the body correlate with metabolic diseases. Animal studies to date suggest the therapeutic potential of IAA, yet its mechanisms of action remain unclear. “Available data are limited to fragmented analyses. We lack comprehensive studies on the response of liver cells to IAA,” emphasizes Aleksandra Uryga, the study's author. As part of her award-winning project, thorough experiments will be conducted to uncover the mechanisms of IAA’s action on various types of liver cells.
"Mapping the molecular mechanisms of IAA's impact on liver cells could pave the way for designing new therapies for patients with liver diseases,” says Aleksandra Uryga. “With a holistic approach, it will also be possible to develop new research hypotheses and therapeutic tools that go beyond current scientific possibilities,” adds the researcher from IIMCB.
Aleksandra Uryga, a doctoral researcher in the Laboratory of Cellular Genomics led by Dr. Aleksandra Kołodziejczyk, has been awarded a PRELUDIUM grant in the NZ2 panel. She will receive PLN 209,960 for her project, Decoding the molecular mechanisms of indole-3-acetic acid influence on liver cells.