New grants for the IIMCB: over 13.6 million PLN for basic research
Researchers from the International Institute of Molecular and Cell Biology in Warsaw have been among the recipients of OPUS 22, OPUS 26, PRELUDIUM 22, and SONATA 19 grants from the National Science Centre. The funding will cover specialized research, including the mechanisms of liver cirrhosis, the molecular basis of neurodegenerative diseases such as Alzheimer's and Parkinson's, and the enhancement of genome engineering methods.
Saving the Liver
Dr. Aleksandra Kołodziejczyk from the Laboratory of Cellular Genomics will focus on the cellular foundations of liver cirrhosis—a dangerous condition caused, among other factors, by liver steatosis, alcohol-related liver disease, viral infection (hepatitis), or toxin exposure. Liver cirrhosis results from the fibrosis of this key organ. In the pathogenesis of this disease, so-called stellate cells produce too much collagen, leading to changes in the extracellular matrix and, consequently, fibrosis. Unfortunately, medicine does not currently have effective antifibrotic therapies.
Thanks to the acquired funds, Dr. Aleksandra Kołodziejczyk's team at the IIMCB plans to thoroughly describe the various types of disease-activated stellate cells and uncover their regulatory mechanisms. The knowledge gained will enable the development of clinical interventions aimed at preventing or mitigating fibrosis. Moreover, since the mechanisms of liver fibrosis show similarities to other organs, this work may pave the way for studying similar pathologies in different tissues.
Understanding Neurodegenerative Diseases
Dr. Lidia Wróbel's research will be dedicated to neurodegenerative diseases, including Parkinson's and Huntington's diseases. These incurable conditions lead to the progressive degeneration and death of nerve cells.
The brain of a person affected by a neurodegenerative disease contains degenerated nerve cells, and their number increases as the disease progresses. The ability to maintain a healthy cellular proteome by removing toxic protein deposits is crucial for the health and survival of delicate nerve cells. As the researcher emphasizes, we still have limited knowledge about the mechanism regulating the effectiveness of nuclear protein degradation in mammals. This highlights the need for a better understanding of the mechanisms maintaining protein balance in nerve cells. We need in-depth knowledge of how the disease state affects this process and—critically—how we can potentially manipulate the protein removal mechanism for therapeutic benefits. The main goal of Dr. Lidia Wróbel's research will thus be to better understand the causes and mechanisms of the development of these neurological disorders at the single-cell level to support the design of targeted pharmacological therapies.
Enhancing Genetic Engineering
The aim of Dr. Zuzanna Kaczmarska's research at the Laboratory of Protein Structure will be to gain a better understanding of the Tn7 transposon mechanism. Transposons, or "jumping genes," are DNA fragments that can move within the genome. In bacteria, transposons carry genes responsible for their virulence and antibiotic resistance. One of the most important groups of transposons is Tn7. Some versions containing the CRISPR mechanism can precisely insert large DNA fragments. Research on Tn7 aims to fully understand its mechanism and utilize it in genome engineering.
As the researcher emphasizes, despite many years of research, knowledge about the Tn7 system is still incomplete. The research will use both biochemical methods and visualizations at various stages of its action. This information will be crucial not only for a full understanding of the Tn7 mechanism but also for harnessing the potential of mobile genetic elements, including CRISPR-related variants, in genome engineering.
Dr. Aleksandra Kołodziejczyk from the Cellular Genomics Laboratory will receive 4,191,920 PLN for the research project "Finding molecular mechanisms behind the activation of stellate cells.”
Dr. Lidia Wróbel, whose new laboratory will open in September, will receive 2,514,102 PLN for the project "Nuclear protein quality control in neurodegeneration."
Dr. Zuzanna Kaczmarska from the Protein Structure Laboratory will receive 2,983,309 PLN for the research project "Comprehensive structural and biochemical studies of Tn7 transposition."
In addition, grants from the NCN waiting list were obtained:
Dr. Magdalena Czeredys: PLN 3,666,661 for the research project "Human iPSC-derived cortico-striatal assembloids as a new model to study neurodevelopmental pathologies induced by mutant Huntingtin.”
Sofiia Baranykova, M.D.: PLN 209,352 for the research project "Looking for mechanisms responsible for the retinal ganglion cell loss in zebrafish stim2 knockout.”
Pratik Kumar Mandal, MSc: PLN 69,540 for a research project: "Exploring the role of Ferroportin-mediated Ca2+ influx in the functional rewiring of macrophages.”
Additional information about the NCN competition: https://tinyurl.com/ymywz3wv