Lenka Dvořáková, GenomMed, Dynamic functional connectivity assessment of traumatic brain injury in rats. Traumatic brain injury (TBI) is an insult to the brain from an external mechanical force. It is important to longitudinally assess the abnormalities in the neuronal networks following the injury for a better understanding of the underlying processes leading to different outcomes. In this study, TBI was induced in male rats and a control group was sham-operated. All animals underwent a series of modern imaging and histological experiments to study the large-scale network alterations.
Flavia Scoyni, GenomMed, Non-coding RNAs network as potential therapeutic targets for central nervous diseases. Neurodegenerative disorders and ischemic brain diseases are one of the first cause of death worldwide. Because of the complexity of these diseases and the biological variability in the patients, only a small fraction of the total patients is benefiting from the available treatments. Yet, a definitive cure is not available. Here we aim at discovering the role of non-coding RNA networks in physiological and diseased brain in vivo to possibly develop novel powerful therapeutic approaches.
Barbara Genocchi, BioMEP, Simulation of astrocytic roles in neural networks and hyperactivity. In the brain, astrocytes control the neuronal activity and ionic homeostasis. In epilepsy, neurons exhibit hyperactivity which can be a result of the uncoupling in the astrocytic network, the decreased glutamate uptake and the unbalanced ionic clearance in astrocytes. To study the effects of these dysfunctions, I computationally model the effect of gap junctions uncoupling on the ionic signalling in astrocytes and on neuronal hyperactivity.
Dao Nguyen, BioMEP, Trajectory Optimization for Robot Arm in controlling the stimulation coil in Transcranial Magnetic Stimulation. Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation that requires excellent accuracy. With the aid of navigation system and robotic systems, TMS accuracy has been improved significantly, but still subjected to inter-trial variations. Therefore, we aim to utilize the application of Robot Arm in controlling the stimulation coil, by developing optimized trajectories for a seven-DoF robot arm in different stimulation protocols, such as motor mapping and TMS related research.
Lingwei Huang, BioMEP, Osteochondral modifications during the development of post-traumatic osteoarthritis in a rabbit model. Osteochondral changes during early osteoarthritis (OA) are poorly known. In this study, we examined concurrent changes in cartilage and subchondral bone at early stages of OA and developed a calcified cartilage segmentation method. We found site-specific changes in subchondral bone as well as in articular and calcified cartilage, with increased cartilage turnover and altered chondrocyte biomechanics. The findings provide novel cues for developing better imaging biomarkers and treatment.
Shuvashis Das Gupta, BioMEP, Developing novel micro-imaging tools to assess calcified cartilage: implications for better understanding of osteoarthritis. Knee osteoarthritis (OA) is the most common joint disease. However, it remains unclear how the calcified cartilage at the osteochondral junction is modulated with OA development. We aimed to develop novel micro-imaging tools for assessing calcified cartilage from the junction in vitro. The experimental findings provide convincing evidence of compositional, structural, and mechanical changes in calcified cartilage during OA progression.
Simone Adinolfi, GenomMed, Nrf2 as regulator of metabolic pathways. Nrf2 is the master regulator of antioxidant response but it also regulates genes involved in glucose and lipid metabolism. We use an Nrf2 hyperactive and deficient cell line to characterize the bioenergetic profile and metabolic fluxes to uncover the pathways regulated by Nrf2. In this experimental setting, Nrf2 deficiency alters the energy metabolism and substrate utilization from glucose and glutamine. The implications of these findings in healthy and malignant cells are discussed.
Golestan Karami, BioMEP, Survival Time Prediction of Brain Tumor Patients by an end-to-end Attention-based multitask 3D CNN. Although many survival time prediction SVM models have shown promising results, there are still several issues. This study proposed a pipeline for predicting survival time using deep learning with minimal pre-processing. We deployed a multi-modality 3D CNN. The model consisted of two stages. The first stage was to extract the important features by the modality-specific network. At the second stage, a fusion network with fully-connected layers was constructed to predict survival.
Sumanta Samanta, BioMEP, Engineering Glycosaminoglycan Derived Hydrogels and Nanoparticles for Biomedical Applications. Glycosaminoglycans (GAGs) are long linear chain polysaccharides that comprise one of the three major biopolymers found in the body. We have exploited their key physiological properties by developing dopamine and gallic-functionalized GAGs (Hyaluronic acid, Heparin, and Chondroitin sulfate A) for a wide range of biomedical applications like Tissue Tissue adhesive bioinks for cornea regeneration, MRI active contrast agents for glioma targeting, Brain mimetic 3D scaffolds for neural network etc.
Hannah Rostalski, GenomMed, Effects of the C9orf72 repeat expansion on neurodegeneration. Frontotemporal lobar degeneration (FTLD) is a devastating neurodegenerative disease. The most common genetic cause of FTLD is an expanded DNA sequence within the C9orf72 gene (C9exp). How the C9exp leads to neurodegeneration is still poorly understood. This study investigates the effects of the C9exp on microglia, which are considered key immune cells of the brain. Also, new genetic markers for identifying C9exp carriers in large genotyped data sets are analyzed.
Rebekka Wittrahm, GenomMed, Elucidating molecular mechanisms of Alzheimer’s disease-associated risk genes. Focusing on genetic variants that decrease or increase the risk of developing Alzheimer’s disease (AD) can provide insights into disease mechanisms. Here, three AD-related genetic risk factors have been studied. One protective variant enhanced the function of mouse immune cells, while the second variant positively altered gene expression in neurons upon inflammatory stress. The third AD risk-reducing variant is currently studied in cell culture models, human carrier-derived tissue and biofluids.
Yike Huang, BioMEP, A DNA origami-based platform for characterizing aptamers. Aptamers are single stranded oligonucleotides that specifically bind to molecules with high affinities. Currently, no standard approach has been developed to measure the binding affinity and the specificity of aptamers. However, results generated by different experimental methods don’t often agree. Herein, we propose a universal strategy for standardizing the aptamer characterization by taking advantages of the DNA origami, which is a technique for nanofabrications by folding DNA strands.
Aarthi Ravindran, GenomMed, Translating Ribosome Affinity Purification Identifies Markers of Atherosclerosis-Associated Smooth Muscle Cells. Atherosclerosis a major contributor to global cardiovascular mortality. The lesion development involves complex interaction between macrophages, endothelial, smooth muscle cells (SMCs). Elucidating contribution of cell types is key to understanding of disease mechanisms. We developed mouse model that allows cost-effective analysis of SMC-specific translatome from any tissue using TRAP-Seq. We demonstrate atherosclerosis associated changes in SMC traslatome and identify novel markers of disease.
Gustavo Orozco, BioMEP, Computational modeling of articular cartilage: predicting post-traumatic knee osteoarthritis. Traumatic knee injuries often involve cartilage lesions and may lead to post-traumatic osteoarthritis (PTOA). Prediction of PTOA progression is challenging and mechanisms leading to the disease are not well known. In this study, degeneration mechanisms were studied by the developed mechanobiological models of the knee joint. These numerical models could aid understanding of causes leading to PTOA and be used as a clinical tool to estimate the effect of interventions on PTOA progression.
Thomas Notermans, BioMEP, Computational modeling of Achilles tendon biomechanics and mechanobiology. My PhD research is focused on computational modeling of the biomechanical and mechanobiological behaviour of normal and healing tendons. These models enables us to investigate mechanobiological processes underlying the evolution of different tendon properties, e.g. tendon geometry, heterogeneous structure, viscoelastic mechanical properties and tissue differentiation. These computer models should eventually help in developing rehabilitation protocols for patients with ruptured Achilles tendons.
Juan Miguel Valverde, GenomMed, Rodent MRI brain segmentation. Segmentation–the process of dividing images into segments–is a typical pre-processing step prior to analyzing images. Particularly in rodent MR brain images, lesion segmentation helps quantifying the volume of the lesions. Segmenting these images manually is, nevertheless, extremely time-consuming and ambiguous, leading to poor segmentations and jeopardizing research reproducibility. This project investigates automatic segmentation methods to produce accurate and consistent segmentations.
Joeri Kok, BioMEP, Biomechanical analysis of hip fracture risk prediction, prevention, and repair. The main focus of my thesis is on the validation of a computational model of a femur replicating a sideways fall. Experiments with high-resolution strain measurements were performed to compare to the models. Similar computational models were used to investigate how much a bone cement can increase the fracture strength of a femur. For the same cement, its ability to increase the stability of a dynamic hip screw was shown with a pullout experiment.
Vahid Farrahi, BioMEP, How adults should distribute their time in the 24-hour day between sleep, sedentary behaviors, and physical activities for a more favorable cardiometabolic health profile? Findings from NFBC1966 device-based measurement of daily activities. The 24-hour day is composed of sleep, sedentary behaviors, and light-intensity and moderate-to-vigorous-intensity physical activity. There is evidence to suggest that each movement behavior is associated with adult health, but it remains unclear how time over a 24-hour cycle should be distributed between all movement behaviors for optimal cardiometabolic health. We discuss how adults could distribute their time in different movement behaviors to improve their cardiometabolic health.
Mustafa Beter, GenomMed, Epigenetic Modulation of Angiogenesis. Angiogenesis is the process of creating new blood vessels from already existing blood vessels.It is a very important process in human body and therapeutic angiogenesis is a promising way to improve some of the diseases such as ischemia. In my studies I use two approaches to modulate angiogenesis: I use adeno-associated viral vectors as transport vehicles for small RNA delivery into cells and I use small epigenetic enzyme modulator compounds. Both ways are promising and study is ongoing.
Ratika Sehgal, GenomMed, Deciphering the systemic and molecular interactions of nutrient-related metabolites in individuals with NASH. The role and underlying mechanisms of nutrient-derived systemic metabolites in NASH are not well understood. Non-targeted metabolite profiling was used to identify such metabolites (leucine, isoleucine, tryptophan, indole-3-propionic acid etc.) in subjects from ongoing Kuopio obesity surgery study. The metabolite specific associations with clinical variables & whole transcriptomics (liver & adipose) provided clues towards probable molecular interactions and will be further validated in-vitro.
Amir Esrafilian, BioMEP, An EMG-assisted Muscle-Force Driven Finite Element Analysis Pipeline to Investigate Multiscale Knee Joint Mechanics in Functional Movements: Towards a Rapid Multiscale Modeling Toolbox. Here, a novel multiscale musculoskeletal-finite element modeling pipeline is established with the focus on a rapid and clinically feasible implementation. To this end, electromyography assisted muscle-force driven finite element model of the knee joint with fibril-reinforced poroviscoelastic cartilages and menisci was integrated into an automated simulation pipeline and used to assess knee joint mechanics in daily activities and rehabilitation exercises in individuals with knee osteoarthritis
Bhanu Prasad Bandlamudi, GenomMed, Disease modelling of Hypertrophic Cardiomyopathy using patient-derived iPSC-CMs. Hypertrophic Cardiomyopathy (HCM) characterized by left ventricular hypertrophy with an elevated risk for sudden cardiac death. It is caused predominantly by sarcomere mutations apart from other nuclear and mitochondrial mutations. Fibrin based 3D engineered heart tissues from patient-derived iPSC- cardiomyocytes are used to characterize different disease-causing mutations including Finnish founder mutations, to study common aberrant signalling pathways involved in the pathogenesis of HCM.
Rowmika Ravi, GenomMed, Exploring at molecular level in Finnish population- The Hypertrophic Cardiomyopathy, a thick heart wall disorder. This project investigates Hypertrophic Cardiomyopathy (HCM), a subgroup of heart muscle disorders, at the molecular level. We explore the genetic cause and metabolic effect of HCM using data on gene sequence, metabolites, and physical examination of 10,197 randomly selected Finnish men in the METSIM (MEtabolic Syndrome In Men) study. Results will increase our understanding of disease mechanism, help in development of population specific diagnostic tool and disease risk management.
Jaakko Syrjälä, BioMEP, Phase coupling of neuronal oscillations in working memory. In our work, we successfully decoded working memory task using MEG source space functional connectivity, supporting the critical role of the phase coupling (theta, alpha and gamma) in WM processing. Our approach, combining across-subject classification and a multidimensional phase coupling metric (MPSI) allowed us to make meaningful interpretations of the task relevant phase coupling patterns and conclude that these patterns are generalisable to new individuals.
Natallie Kajevu, GenomMed, Systems biology—based drug repositioning to promote recovery from Traumatic Brain Injury: in vitro and in vivo validation. My project aims at mitigating severity of post-TBI complications by using systems biology approach to select neuroprotective drugs that can promote recovery from TBI. Therapeutic effect of selected drugs was assessed in vitro. Currently, experiments are on-going to assess in vivo effect of promising drugs. Successful completion of my project could improve efficacy of treatment offered to TBI patients.
Ruhunur Özdemir, BioMEP, A connectivity study on anterior nucleolus of the thalamus deep brain stimulation surgery (ANT-DBS) in epilepsy. We present a study that sheds light on the mechanism of ANT-DBS using HARDI imaging technique. HARDI image analysis techniques; MSMT-CSD and SSST-CSD tractography models are utilized to demonstrate the major white matter connections, which are involved in the control of epileptic seizures, in the limbic system. We particularly demonstrated the connections from mamillary to subiculum and hippocampus via fornix and accurate reconstruction of MTT from the mammillary to the ANT for the first time
Nataliia Martyniuk, BioMEP, Resolving functional connections between visually guided behavior and the retinal signals in dim light. All visual information available to the brain is encoded in the spike trains sent by retinal output neurons, ganglion cells. I study how dim light stimuli are encoded by the most sensitive On and Off ganglion cell types, and how their spikes are read out by the brain to guide visual behavior. I show that the brain relies on On cells in encoding light increments and on Off cells in encoding light decrements. This shows a remarkable distribution of labor in retinal coding already at starlight.
