Donations Granted

Approximately 5,000 cases of acute lymphoblastic leukemia are diagnosed annually in children and adolescents in Europe. With current treatment, approximately 80% of T-ALL and 90% of B-ALL can be cured, but the treatment is lengthy and has significant side effects. Our research project aims to develop more effective and less toxic combination and immunological therapies. We are searching for and optimizing new drug treatments targeting the signaling pathways of B- and T-cell receptors and the metabolism of leukemia cells. We harness the body’s own immune system to enhance treatment response and use multidimensional data as a patient-specific map for an AI model that predicts treatment outcomes. The project’s results aim to reduce treatment-related side effects, improve the prognosis of leukemia, and increase knowledge of the disease’s biology.

Artificial intelligence agents (AI agents) are computer programs or information systems that are capable of performing independent and intelligent actions while pursuing a certain goal. A critical uncharted area of AI agents relates particularly to their unethical and unwanted behavior. AI agents can be harnessed to deceive people, they can group together and be set free to carry out criminal activity, in such a way that it is not possible to stop them. The aim of the project is to identify, mitigate and prevent the negative effects of AI agents. The project investigates various manifestations of malicious artificial intelligence such as chatbots, service robots, and metaverse avatars.

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.

Colorectal cancer ranks as the second leading cause of cancer-related deaths, highlighting a significant social and economic need for improved treatments. The disease’s progression results from interactions between cancer cells and surrounding cells, such as fibroblasts. While conventional anticancer drugs primarily target cancer cells, fibroblasts also play a crucial role in cancer development. This research investigates the function of fibroblasts cells in colorectal cancer progression. The objective is to identify properties of fibroblasts that favor cancer, thereby aiding the development of more effective treatments and preventative measures for genetically predisposed populations.

Our research focuses on male germ cells and their unique function in the intergenerational transmission of information and maintenance of life. Our main research interest is the epigenome, i.e. the environment that controls gene expression, and its regulation and influence on sperm function. Sperm epigenome has a central role in the maintenance of fertility, and changes in the epigenome can also have more far-reaching, intergenerational effects on the offspring. Our results will help us to understand the factors behind male infertility, but also the effects of father’s environmental exposures and lifestyle on offspring health, therefore opening novel possibilities for disease diagnosis and prevention.

Double-stranded RNA viruses infect a wide range of life forms from bacteria, fungi, plants, to animals. The group includes many significant pathogens such as bluetongue virus in sheep, rice dwarf virus, and human rotavirus. Despite the wide host range, these viruses are functionally and structurally similar. In this project, we investigate double-stranded RNA viruses belonging to the cystovirus group and utilize cryogenic electron microscopy (cryo-EM) to three-dimensionally image the key stages of the viral life cycle at the molecular level. The results shed light on the dynamics and evolutionary origins of biological membrane structures. New knowledge of the life cycle also supports the development of biotechnological applications based on cystoviruses.

This project aims to explore the biochemical basis of information processing in the brain, focusing on the role and function of prion-like proteins that undergo structural changes during synaptic activation. We will investigate how these prion-like proteins self-assemble in experimental models of memory formation and whether their structural changes activate protein synthesis programs required for memory consolidation in activated synapses. This work will provide insights into the biochemical mechanisms of information processing in synapses and offer new perspectives on the link between prion-like proteins and neurodegenerative diseases associated with memory impairment.

In this project, we generate optogenetic tools for mammalian cells and apply them to breast cancer models. Optogenetics is a field of research that controls cellular processes with light. The tools generated in this project are based on red light-sensing bacterial photochromes and enable cell death (apoptosis) of cancer cells induced by red light. The resulting apoptosis tools will be applied to breast cancer cell models and assayed for their applicability for cancer therapy. Our optogenetic tools will provide a non-invasive alternative for current cancer treatment methods, as they can be controlled with red light through patient’s skin. They have also potential for multitude future applications in basic research, biotechnology, and biomedicine.

Double-stranded RNA viruses infect a wide range of life forms from bacteria, fungi, plants, to animals. The group includes many significant pathogens such as bluetongue virus in sheep, rice dwarf virus, and human rotavirus. Despite the wide host range, these viruses are functionally and structurally similar. In this project, we investigate double-stranded RNA viruses belonging to the cystovirus group and utilize cryogenic electron microscopy (cryo-EM) to three-dimensionally image the key stages of the viral life cycle at the molecular level. The results shed light on the dynamics and evolutionary origins of biological membrane structures. New knowledge of the life cycle also supports the development of biotechnological applications based on cystoviruses.

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.

Schizophrenia (SCZ) affects 1% of the population and is driven by excess striatal dopamine (DA). However, it is unknown what increases brain DA in SCZ, thus we are unable to define effective treatment. Recently, my laboratory found that excess of one of the strongest DA neurons function enhancing proteins GDNF is likely to drive excess DA in 20% of SCZ patients, allowing development of new drugs and biomarkers. My research for the next four years has three main Objectives. First, I aim to develop our drug candidates into patentable drug leads to then aim for clinical trials. Second, I aim to better stratify GDNFhigh SCZ patients to enhance insight into excess GDNF driven SCZ. Third, I aim to define longitudinal biomarkers for disease and current treatment evaluation with the focus on GDNFhigh patients.

A natural compound, creatine is highly needed for the energy homeostasis, particularly in the brain and heart muscle. Curiously, creatine transportation to the cells is impaired in many cardiovascular diseases and central nervous system CNS diseases. Therefore, in this science-renewing project, we are seeking to find new solutions to circumvent this problem and deliver creatine to its target cells (neurons and cardiomyocytes), more effectively via other transport mechanisms, which could aid in the prevention and treatment of many CVD and CNS diseases. Most importantly, the created know-how and methodology can be applied to other CVD or CNS drugs and leveraged to other therapeutic areas after the project.

Sleep is a vital physiological process, compulsory for mental and physical recovery. However, the analytic practices have not evolved, and sleep staging is still restricted to human pattern recognition and 30-second time intervals. Therefore, the main objective of this project is to establish a robust and fully automated whole-body sleep staging model that merges information from physiological systems and the brain´s electrical activity with high temporal resolution. This can enable comprehensive and clinically relevant evaluation and classification of healthy and diseased sleep.

Diabetes mellitus (DM) is alarmingly increasing and novel therapeutic approaches for DM are needed. In type 2 diabetes (T2D), chronic endoplasmic reticulum (ER) stress is a central event for beta cell failure, insulin resistance, and vascular dysfunction. We found that MANF by relieving ER stress reduces death of insulin producing beta cells in mice. In addition, small molecule compounds mimicking MANF reduce detrimental ER stress in cellular models. We aim to test whether MANF and mimetics inhibit T2D development and its complications in a mouse T2D model by reducing ER stress. The mechanisms of action will be tested on beta cells and tissues, and human cell lines in T2D settings. Our holistic therapeutic approach based on decreasing cellular stress may treat T2D and its complications.

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.

Leishmania and Trypanosoma parasites cause diseases such as leishmaniasis and African sleeping sickness. There are no optimal drugs for these diseases, and the parasites have developed resistance to several compounds already in use. Actin is a central protein found in all eukaryotes. We recently found significant differences in the structures of actin between parasites and humans. By combining Ilpo Vattulainen’s group’s expertise in computational biology, and Pekka Lappalainen’s group’s expertise in actin-related structural biology and biochemistry, we aim to identify compounds that inhibit parasite actin without affecting the function of human actin. Such compounds are good new drug candidates for the treatment of diseases caused by these parasites.

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.