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Neurological disorders like Alzheimer’s and Parkinson’s disease have significant personal costs for those affected and pose a considerable socioeconomic challenge worldwide. There are no treatments available to modify disease progression. Several neurological disorders have a common defect in a cellular recycling process termed autophagy. The project aims to study a recently discovered group of patients with genetic impairments in autophagy, to understand how they adapt and survive despite defects in a key homeostatic mechanism. The research aims to uncover new knowledge and therapeutic targets that could help defeat degeneration.

In this project, we map cellular RNA structures in colorectal tumours, determine the role of RNA-protein interactions in mediating oncogenic RNA folding, and uncover the relationship between RNA structures and oncogenic gene expression. RNA structure targeting molecules are designed to uncover their clinical potential as cancer medicines. Understanding oncogenic RNA structures opens a new avenue for the design of RNA structure targeting cancer medicines that have broad applications beyond colorectal cancer. Thus, the proposed research will help realising the clinical potential of RNA in cancer therapy and enable the rationale design of RNA structure targeting therapeutics that could be transformative in combatting cancers currently incurable.

Early experiences shape brain development and influence the risk for developing neuropsychiatric problems later on in life. This project aims at comprehensive characterization of the mechanisms by which early life stress affects neural circuits regulating emotional learning and behaviour in rodent models. In parallel, opportunities for preventing the pathological development are explored, focusing on kainate receptors, a unique family of glutamate receptors implicated in development and plasticity of limbic neural circuits. We expect the results to provide novel clinically relevant information on neurodevelopmental disorders and prospects for their targeted treatment.

Viruses with RNA genomes cause most of the emerging and re-emerging infectious disease epidemics. The project aims to establish a comprehensive view of host interaction during virus replication by identifying host proteins that assist in virus replication. We aim to understand the specific actions that each host factor performs during virus replication. The proteins could assist e.g. in the modification of host cell membranes, as viruses rearrange the membranes to create protective replication vesicles. The host proteins important for virus replication are attractive new targets for antiviral drugs that could act broadly against several virus families.

Diagnostics and treatment options that are under development for neurodegenerative disorders (NDDs) are based on detecting accumulation of pathological proteins (such as beta-amyloid) and early clinical symptoms (mild cognitive impairment, MCI). Problematically, a substantial proportion of elderly healthy individuals who do not have dementia may also show protein accumulation in their brain with concomitant cerebrospinal fluid biomarker alterations. Furthermore, not all individuals with MCI eventually develop a neurodegenerative disorder. Hence, new approaches are needed in the diagnostics, prognostics, treatment, and monitoring of treatment efficacy in NDDs.

Disturbances in the neurotransmitter systems (NTS) are known to be the first detectable changes in NDDs, and these changes occur before irreversible brain atrophy. Today, transcranial magnetic stimulation (TMS) offers possibilities to conveniently measure the NTS changes. Moreover, our previous studies show that these changes can be modified in the brain of Alzheimer’s disease patients by using transcranial alternating current stimulation (tACS).

This project aims to solve challenges in the early detection and prognostics of NDDs by combining TMS measurements, novel fluid biomarkers, and global analyses of brain activity. The project is expected to provide new tools for early and personalized NDD diagnosis and enable accurate patient selection for therapeutic studies. Furthermore, we aim to prove tACS as a novel treatment approach for NDDs.

A member of the Finnish disease heritage, GRACILE syndrome is one of the most severe mitochondrial diseases with onset before birth. Utilizing experimental models of GRACILE syndrome, our research aims at elucidating novel disease mechanisms in mitochondrial diseases and testing treatments. This project is based on our recent findings showing that the oncogene c-MYC drives harmful cell proliferation, leading to premature aging of tissues and a progeroid disease in the mouse model. We aim to dampen this process directly by genetic means and indirectly with drug molecules, hoping to slow down the detrimental accumulation of senescent cells in the tissue and attenuating disease progression.

The project investigates the role of the brain’s immune cells, microglia, in frontotemporal dementia. Previous studies suggest alterations in the immune system of frontotemporal dementia patients, but the role of microglia in different hereditary or clinical forms of the disease is not understood. The aim is to shed light on the cell biological and functional changes taking place in microglia and their effects on the function of neurons and their connections, synapses. The research utilizes microglia and neurons produced by stem cell technology from patients and their co-cultures, as well as blood and cerebrospinal fluid samples. The aim is to better understand the disease mechanisms of different subtypes of frontotemporal dementia and to identify new research-based biomarker and drug targets.

Alzheimer’s Disease (AD) affects over 50 million people globally and the AD-related death rate in Finland has nearly doubled in the past decade. Despite active research, there’s no cure for this disease. The elevated complement cascade of the immune system in AD brains contributes to the elimination of synaptic connections, crucial for brain function. However, the primary step in this pathway has remained elusive. Our research investigates the interplay between complement and neuronal ion transporters aiming to safeguard neurons from inflammatory-induced synapse loss. Dysregulation of complement may trigger the synapse loss leading to an imbalanced neurotransmission. Due to this novel approach, this study has the potential to open up new avenues for alternative treatments and drug discovery.

Alzheimer’s disease is becoming a major health care problem with aging population. Current therapies cannot stop or delay the neuronal death that occurs in the disease, and therefore, novel drug targets and candidates are urgently needed. It is not known what eventually initiates the neuronal death in Alzheimer’s disease but there is growing evidence that beta-amyloid – the main component of Alzheimer’s plaques – damages cellular transport systems that then initiates the accumulation of other protein, tau, in the cells. This eventually leads to neuronal death. The aim of the study is to clarify if we can reduce the tau accumulation or restart the cellular transport by targeting protein phosphatase 2A (PP2A) with small molecules.

In Finland, more than 2 billion clinical lab tests are conducted every year, marking this as a major healthcare service and cost factor. Current approaches to blood testing in primary and occupational healthcare are opportunistic and fail to consider the full richness of health data or to integrate genetic information. Our hypothesis is that AI can be successfully employed to optimize laboratory testing by identifying individuals who are likely to have abnormal values and would therefore benefit most from a blood test. By using registry and genetic data, we aim to predict abnormal creatinine values and will validate our approach by recalling 2,000 individuals for potential chronic kidney disease screening. This could make testing more equitable and efficient in Finland.