Research groups that operate wholly or partly under the Molecular and Integrative Biosciences Research Programme.
The groups are presented in alphabetical order by the last name of the group leader.
Our ability to see in vastly varying conditions depends critically on the outstanding performance of vision. Vision begins in the neural circuits of the retina, which operates with a remarkable fidelity. We study novel signal processing mechanisms and their adaptive dynamics at the synaptic and cellular-element level across the entire neural circuit of the retina.We do so by combining a battery of techniques allowing precise manipulations of local signal and noise statistics in a well-defined retinal circuit relying on genetically modified mice, molecularly tailored artificial visual pigment molecules, and cutting-edge electrophysiological recording techniques. We seek to understand the functional implications of novel retinal signal processing mechanisms by correlating our results with the output of the entire visual system measured in mouse behavioral experiments and human psychophysics experiments.
Around 15% of the proteins produced in our bodies are destined for the cell surface and undergo rapid recycling. Control of this dynamics is essential for cellular function, with disruptions linked to multiple diseases. One key process in maintaining this equilibrium is endocytosis. We focus on clathrin-mediated endocytosis, the predominant endocytic route in most cells. The clathrin machinery also forms stable structures called flat clathrin lattices. We recently discovered that these structures are essential for the establishment of reticular adhesions. Our research aims to elucidate the interplay of clathrin structures with the actin cytoskeleton and cellular adhesions. To tackle these questions, we combine state-of-the-art techniques in cell biology, biochemistry, and structural biology.
Our work aims to understand the structure, assembly and function of biological macromolecule complexes. We embed unstained, unfixed specimens in vitreous ice to preserve their structures. Transmission cryo-electron microscopy is then used to visualize the specimens, but the images recorded are difficult to interpret because they are projections of the specimen degraded by noise. Thus we computationally combine images of the specimen viewed from different angles enabling us to reconstruct a three-dimensional model. Any inherent symmetry present in the structure is also used in this averaging. This method is particularly useful for objects that are too large, unstable or variable to be studied by X-ray crystallography or NMR, such as enveloped viruses.
The Fagerholm group studies the role of leukocyte integrins in various immune reactions. We are interested in the in vivo roles and regulation of leukocyte beta2-integrins in a healthy and dysfunctional immune system. The immune system functions to protect us from disease and is therefore fundamental for human survival. However, especially in “clean” Western societies, the immune system also poses a significant threat to the individual, as immune cell mediated diseases such as autoimmunity and allergy are becoming increasingly common. We are interested in leukocyte beta2-integrins, important cell surface receptors in leukocytes which regulate both adhesion and signalling in immune cells.
The Gahmberg Group has an extensive know-how in modern biochemistry, molecular biology and cell biology, and cooperates with several internationally recognized research groups. Several foreign graduate students, postdoctoral fellows and senior scientist have worked in the group. Some are currently members in the research projects.
Currently, the group focuses on two major projects: 1) Regulation of leukocyte integrin activity by phosphorylation, and 2) Role of hypoxia in tumor growth. We have found that a novel integrin and hemoglobin facilitate cancer growth.
We study different integral- and membrane-associated proteins. Our goal is to understand their structure and mechanism of action. Our primary techniques include X-ray crystallography, cryo-electron microscopy, transport and other functional assays. We also dabble (via collaborators) with FRET, PELDOR and electrometric measurements.
We study how animal body responds to changes in nutrition. Our goal is to understand how specific macronutrients in the diet, such as sugars and amino acids, affect energy metabolism, growth and stem cell function. Uncovering the regulation of these physiological processes will bring new insight into human diseases associated with nutrition and metabolism.
Our research in the Laboratory of Structural Biology aims at understanding the structure and function of biological macromolecules and their complexes, such as those involved in cellular cargo transport, protein folding, cell-cell contacts and viral infection. We strive to decipher basic principles in their assembly and function by structural biology methods, notably cryogenic electron microscopy (cryo-EM). We are also actively developing computational data analysis and sample tagging and capture methods for cryo-EM. Detailed mechanistic understanding of proteins involved in disease is informing rational design of therapies.
Our research strategy is based on an integrative approach, where physiological and pathophysiological mechanisms are investigated from the molecular and cellular level to the whole organism. We also aim to bring a strong evolutionary perspective in the study of CNS disorders. As pointed out in reviews (Kaila et al., 2014a, b), disease processes including those related to IRP functions have both adaptive and maladaptive components. Indeed, according to Rudolph Virchow’s famous statement, disease is “only a manifestation of life under modified conditions, operating according to the same laws that apply to the living body at all times”.
Our body is constantly repaired and renewed by tissue specific stem cells, which produce cells undertaking specialized functions, and new stem cells maintaining the future renewal capacity. In a young body, such tissue stem cells can easily counter the wear and tear of everyday life by replacing damaged cells with new ones. However, as we age, capacity of stem cells declines, and the resulting drop in tissue repair manifests as the functional decline associated with aging. Our goal is to understand why stem cell activity deteriorates with age, and to develop stem cell based strategies targeting aging related diseases and ailments.
The Kilpinen group is interested in cellular genetics and the cellular basis of developmental and other brain-related disorders. We use human induced pluripotent stem cells as models, and combine computational and experimental methods to study how genetic variation causes variability in cell phenotypes and contributes to differential susceptibility to diseases, both common and rare. The group is part of the Helsinki Institute of Life Science (HiLIFE), Faculty of Biological and Environmental Sciences, Institute for Molecular Medicine Finland (FIMM) and the Neuroscience Center.
The group has biomedical and ecophysiological projects. The roles of lipids and fatty acids are studied in human vital functions and pathophysiology as well as in environmental adaptation and feeding ecology of animals. In addition to basic research we carry out applied projects. For example, together with our collaborators we develop functionality markers for stem cells used for transplantations, and improve methods for monitoring the diets of wide-ranging aquatic animals, such as seals and seabirds. The main methods used are mass spectrometry, chromatographic techniques and multivariate statistical analyses.
The actin cytoskeleton provides force for dynamic cellular processes, such as motility, morphogenesis, cell division, endocytosis, and phagocytosis. The organization and dynamics of actin filaments must be precisely controlled during these processes, and consequently defects in regulation of the actin cytoskeleton lead to various diseases including cancer progression, as well as neurological and immunological disorders. Our group uses a wide range of biophysical, biochemical, cell biological, and genetic approaches to uncover the general principles underlying regulation of the actin cytoskeleton, and to reveal how defects in actin dynamics affect the physiological functions of cells.
The group focuses on studying the mechanisms guiding activity-dependent development of glutamatergic circuitry in the limbic system and in particular, the roles of ionotropic glutamate receptors in this process. So far, we have identified several novel features related to functions and regulation of AMPA and kainate-type glutamate receptors at the developing synapses. Our current research aims to understand in detail how these mechanisms contribute to development and fine-tuning of the neural circuits underlying behavior under physiological and aberrant conditions, such as early life stress.
Stem cells are essential for maintaining tissue health. The functionality of stem cells declines during aging. This decline contributes to physiological deterioration during aging and can lead to diseases.
Our research aims to understand how stem cells age and whether we could use this knowledge to develop therapeutic approaches to maintain stem cell function during aging and in disease prevention.
Aging is the greatest risk factor for numerous diseases, including cardiovascular disorders, neurodegenerative conditions, and cancer. In addition to increasing disease susceptibility, aging also reduces quality of life by impairing physical function, cognitive capacity, and resilience to stress. The aim of our research is to identify novel dietary supplements, biomolecules, and drug candidates that promote healthy aging by delaying the biological aging process.
Our research is focused on finding molecular mechanisms linking metabolism and cellular signaling pathways in experimentally challenging and topical settings, such as in vivo stem cell populations. The Mattila lab is driven by curiosity to use quantitative data for uncovering processes linking metabolism and signaling in complex systems. As an in vivo model for metabolic and physiological processes, we use the ever so fascinating fruit fly Drosophila melanogaster. Scientists in the Mattila lab are playful, sarcastic and empathetic. We work for the love of science and for the excitement of making discoveries!
In our work, we aim to reveal the developmental correlates of altered brain function in psychiatric disorders with motor behavior and attention deficiency. Many neurodevelopmental disorders, i.e. autism spectrum disorder, attention deficit/hyperactivity disorder and obsessive-compulsive disorder, are accompanied by pathologies in motor behavior, including uncoordinated movements and repetitive actions. The main brain structure responsible for the motor learning and habit formation is striatum. We study the formation of synaptic connections in striatum during early postnatal ontogenesis in healthy organism and in animal models of neurodevelopmental disorders. In our experiments, we use a number of transgenic mouse lines for both ablation of the genes of interest and expression of reporter proteins in specified neuronal populations. Our methods include in vitro electrophysiology, immunocytochemistry and behavioral tests.
Our research aims at molecular level understanding of the functions of viruses and how viruses interact with their host cells. In addition, we investigate how sequence or structural similarity reflects the common evolution of viruses which are infecting different cellular domains of life. We are part of the Molecular and Integrative Biosciences Research Programme at the Faculty of Biological and Environmental Sciences.
The gastrointestinal epithelium undergoes rapid and continuous renewal, a process tightly regulated by surrounding stromal cells, such as fibroblasts. Disruption of this regulatory balance contributes to pathologies, such as colorectal cancer, one of the most prevalent and deadly malignancies. In Ollila lab, we investigate the identities and functions of the various fibroblast subtypes within the gastrointestinal tract, and study the molecular mechanisms facilitating the communication between different cell types. In addition, we study the mechanisms of fibroblast rewiring during tumorigenesis, transforming from homeostatic to cancer-promoting cells. Our studies deepen the understanding of stromal-epitelial crosstalk, potentially uncovering novel therapeutic approaches for gastrointestinal pathologies such as colorectal cancer.
We study the genes and mutations and pathogenetic mechanisms causing congenital myopathies, with the main focus on nemaline myopathy.
Mood, motivation and movement are regulated by circuits in the anterior brainstem – an evolutionarily old part of the brain. We are interested in the neuronal cell types of the brainstem, and how their heterogeneity arises during embryonic development. In particular, we study the gene regulatory cascades establishing distinct neuronal identities. Information on brainstem neurons, and their subtypes, is essential for understanding the function of the brainstem circuits and the vital behaviors they regulate.
Our current research examines the molecular mechanisms that maintain the survival and function of hair cells and neurons of the cochlea. We study how these homeostatic mechanisms operate under normal conditions and how they respond to environmental stressors, particularly to loud sounds. Based on this knowledge, we study if cellular stress could be manipulated for therapeutic purposes to protect against hearing loss.
Our research aims at molecular level understanding of viral replication mechanisms and self-assembly pathways. These functions are critical in viral disease development and important targets for antivirals. The basic molecular virology research carried out in our laboratory has also led to innovations in the field of RNA interference facilitating the development of new antiviral therapeutics and novel crop protection strategies. We are part of the Molecular and Integrative Biosciences Research Programme at the Faculty of Biological and Environmental Sciences.
Cells and tissues are not static structures, but during development they change their size and shape and migrate. Plasticity of cells and tissues also requires remodeling of cytoskeleton in order to orchestrate their adhesive, protrusive and contractile properties. We want to understand how disassembly of actin cytoskeleton is regulated in cells that are changing their shape or moving.
We are dedicated to improve the life of patients with mitochondrial disease by understanding the mechanisms underlying these maladies that have no treatment option.
Myelin is an insulating substance that wraps around axons, enabling the fast and efficient transmission of electrical impulses in the nervous system. Upon damage, myelin sheath can be functionally restored through a regenerative process known as remyelination. However, in demyelinating diseases, such as multiple sclerosis (MS), remyelination fails. The Translational Regenerative Neurobiology Group (TReN) aims to study how remyelination works and to explore why it fails during MS. Our final goal is to design and develop regenerative therapies for the treatment of demyelinating diseases.
Our research focuses on atmospheric transmission of viruses and other bioaerosols. We study their viability and aerosolization mechanisms, dispersion pathways and the ability to nucleate ice. We are also interested in how climate change affects the transmission, viability and biodiversity of atmospheric microbes.
The goal of our research is to explain how dynamic alterations in protein folding and assembly states regulate the phenotypic plasticity of cells and organisms. This information is highly relevant for the understanding of fundamental biological processes ranging from development to adaptation and aging, and has implications for a number of diseases, including neurodegeneration and cancer.
Why should we care about tRNA modification?
Transfer RNA (tRNA) is at the heart of translation — the process at which the genetic code of an organism is deciphered into functional machines, i.e. proteins. In this process, the tRNA molecules work as adapters that proofread the code and, upon a successful match, add the correct amino acids, i.e. the building blocks that make up proteins. For this intricate process to function correctly, tRNA molecules need to be chemically modified at key positions of the molecule. This is achieved by specialized tRNA modification enzymes acting alone or as part of complex pathways. These post-transcriptional modifications provide structural integrity to the tRNA molecule and more importantly, they regulate the accuracy and speed of translation.
The RNAcious laboratory studies the role of tRNA modifications as modulators of translation, broadly exploring their impact on topics such as host-pathogen interaction, cancer formation, tissue differentiation and aging, and as tools for optimization of bioproduction systems.
Eukaryotic and prokaryotic cells produce minute (40-1000 nm) membrane vesicles that are released into the local environment. These extracellular vesicles (EVs), including exosomes and microvesicles, contain a multi-molecular cargo of proteins, nucleic acids, lipids and metabolites. Together with the number of EVs, this “EVome” reflects the state of the organism and is subject to change upon environmental cues and the activation state of the cell. EVs may thus target recipient cells by e.g. the transfer of genomic material, or influence them by signaling lipids in the EV membrane. EVs have already been shown to function in various roles of cell-cell communication, in processes ranging from the regulation of immune responses – both good and bad – to cancer metastasis. The novel mechanism of cell signaling via EVs is a hot topic of contemporary cell biology. At the same time, there is a fast increasing interest in the use of EVs in diagnostics (liquid biopsies), therapeutics, and in drug delivery. The composition and quantity of EVs changes in many diseases, and is actively studied in cancer, opening possibilities for the use of EVs as early diagnostic or prognostic indicators. Furthermore, EVs may carry much of the therapeutic potential of stem cells and could be utilized in the treatment of complex diseases.
We are interested in the basic mechanisms involved when bacteria infect the human host. The research group studies, at the molecular level, the function of bacterial surface proteins and protein appendages involved in infectious processes and bacteria-host interactions. A special focus is on bacterial pathogens causing recurrent urinary tract infections and newborn meningitis as well as on health-promoting lactic acid bacteria. We also apply bacterial proteins and protein complexes biotechnologically for medical or diagnostic purposes.