PhD students from the IEM CAS were successful in the GA UK grant competition: Five projects succeeded

The Charles University Grant Agency (GA UK) recently published the results of this year’s competition, and our Ph.D. students have again shown that they are among the best. A total of 5 projects of the IEM CAS received support across various fields of research.

In the 22nd round of the GAU competition, a total of 818 new projects were submitted. 261 of them were supported, which represents a 32% success rate.

Congratulations to all successful researchers and we keep our fingers crossed for the realisation of the projects! For those who did not receive support this year, we wish you the determination to continue. Failure is a natural part of scientific work; the life and career path of a scientist is simply a long run, but definitely worth it!

More information can be found on the Charles University website (open in a new window).

Overview of the projects

Faculty of Medicine in Pilsen, Charles University

The project aims to investigate changes in mitochondrial DNA and the composition and diversity of the gut microbiome, in order to understand their individual roles and the role of their interactions in the initiation, development and progression of diseases (obesity and colorectal cancer). By identifying these mechanisms, new biomarkers and targets for mitochondrially targeted therapies for these diseases can be discovered. The project will analyze a range of biological samples, including peripheral blood, stool, and solid tissue, such as intestinal mucosa, intestinal adenoma, and carcinoma tissue. Samples will be collected from healthy control subjects and from patients with obesity, intestinal adenomas and carcinomas. Experimental methods used will include nucleic acid isolation, reverse transcription, quantitative and digital PCR, next-generation sequencing, and advanced statistical and bioinformatic analyses.

2nd Faculty of Medicine, Charles University

Parvalbumin interneurons are important key players in stabilizing neuronal networks. They are vital for cognitive functions, such as learning and memory. Dysfunction and loss of PV+ interneurons are associated with neurological disorders, including epilepsy, Alzheimer’s disease, and schizophrenia. Given the limited neurogenesis in the adult human brain, neuronal reprogramming has emerged as a promising strategy for replenishing neuronal loss. This project focuses on reprogramming murine glial cells into parvalbumin interneurons in vitro by upregulating interneuron specific genes. Newly formed neurons will be analyzed using real-time qPCR, immunocytochemistry and patch-clamp.

2nd Faculty of Medicine, Charles University

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the motor system, leading to muscle atrophy and eventually to respiratory failure and death. The etiology and pathophysiology of ALS remain poorly understood, hindering the search for a cure. One of the hallmarks of ALS pathology is neuroinflammation, which involves the activation of microglia in the central nervous system (CNS). Additionally, emerging evidence suggests that ALS is associated with alterations in the gut microbiota and intestinal inflammation, indicating a potential link through the gut-brain axis. These findings highlight microbiota transplant (FMT) as a therapeutic approach for ALS.

We aim to test the efficacy of two FMT protocols with continuous evaluation of muscular strength, motor coordination and body weight, and monitoring of lifespan. To analyze whether a reduction of inflammation accompanies the alleviation of the ALS phenotype, we will immunohistochemically analyze brain and spinal microglia. Furthermore, we are going to analyze the cerebrospinal fluid samples regarding microbial metabolites translocated from the gut, neurotransmitters, cytokines and neurotrophic factors, to evaluate the extent of inflammation. Moreover, we aim to clarify the effect of FMT treatment on the function of the nervous system at the cellular and molecular level, especially the activation of microglia in the brain and spinal cord and its subsequent effect on the function and viability of motor neurons and astrocytes. Immunohistochemistry will also be used to evaluate the beneficial effect of FMT on the loss of motor neurons. We hypothesize that FMT treatment has the potential to delay symptom onset, improve motor function, and prolong the lifespan by reducing the neuroinflammation. Confirmation of this hypothesis would make FMT a promising therapeutic approach for ALS and other diseases associated with neuroinflammation.

Faculty of Science, Charles University

Stroke is a leading cause of death and disability globally, with limited treatment options. One of the potential therapeutic targets is the mTOR signaling pathway, which modulates several processes related to post-ischemic damage. The proposed project will focus on the role of the mTOR signaling pathway in NG2 glia, cells with a wide differentiation potential, in which this pathway is most likely key for the processes of their activation, migration and differentiation into different cell types. In the acute phase of cerebral ischemia, these cells migrate to the site of damage, proliferate and can give rise to new oligodendrocytes or astrocytes and support angiogenesis.

The project’s aim is to investigate in detail the role of the mTOR signaling pathway in these processes and to confirm the protective effect of its modulation in NG2 cells during ischemic brain damage. Stroke will be modeled in mice by middle cerebral artery occlusion. Changes in the expression of individual components of the mTOR signaling pathway in NG2 glia after ischemic damage will be evaluated using transcriptomic analysis, and immunohistochemical analysis will be used to confirm the expression changes. The effect of the specific modulation of the mTOR pathway in NG2 cells will be tested using conditional mouse models. The functional changes of NG2 cells will be investigated using the patch-clamp method, and the overall functional impact using behavioral tests.

2nd Faculty of Medicine, Charles University

The blood-brain barrier (BBB) is a complex cellular interface that separates the central nervous system (CNS) from the blood supply, which in addition to nutrients contains neurotoxic substances and pathogens. Damage to the BBB is part of the pathophysiological processes of several injuries and diseases. The absence of effective treatment contributing to the restoration of the protective function of the BBB leads to secondary damage to the nervous tissue.

Activation of the Wnt/b-catenin signaling pathway after ischemia has recently been shown to be a promising therapeutic approach to restore BBB integrity. This signaling pathway is activated in embryogenesis by neural precursors producing Wnt glycoproteins1, which are carried through the bloodstream by extracellular vesicles (EVs). The therapeutic potential of different types of Evs and the activation of the Wnt/b-catenin signaling pathway after BBB damage have been demonstrated in the past. But not together. This project aims to study the protective effect of EVs derived from neural precursors in the context of ischemic damage to the BBB and activation of the Wnt/b-catenin signaling pathway. A set of immunocytochemical stainings and Western blots will monitor changes in tight junctions between endothelial cells. RT-qPCR tracking miRNAs inside Evs and the subsequent validation of the effect of these miRNAs on the activation of the Wnt/b-catenin signaling pathway will be performed.