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Doctoral defence of Flavia Scoyni, MSc, 23 Feb 2024: Unlocking the potential of non-coding RNAs in regulating neurodegeneration

The doctoral dissertation in the field of Molecular Medicine will be examined at the Faculty of Health Sciences at Kuopio campus. 

What is the topic of your doctoral research? Why is it important to study the topic?

The topic of my doctoral research revolves around the exploration of non-coding RNAs (ncRNAs) and their crucial role in regulating gene expression, particularly in the context of neurodegenerative diseases. Understanding the intricate mechanisms by which these ncRNAs operate is essential for uncovering the underlying causes and progression of such conditions. 

Studying ncRNAs is of paramount importance due to their significant implications in pathophysiological processes. These molecules participate in complex feedback circuits with other ncRNAs, influencing gene expression and contributing to disease development. By delving into the roles of ncRNAs, my research aims to shed light on the onset and progression of neurodegenerative disorders, providing a deeper understanding of their molecular underpinnings.

Furthermore, investigating the diagnostic and therapeutic potential of ncRNAs holds promise for revolutionizing disease management. Leveraging the stability and detectability of ncRNAs in biological samples can facilitate the identification of aberrant expression patterns, potentially serving as biomarkers for early disease detection, classification, and treatment monitoring. Additionally, by exploring the therapeutic capabilities of ncRNAs, personalized medicine approaches can be developed, tailoring treatments based on individual ncRNA expression profiles to optimize patient care and enhance clinical outcomes.

What are the key findings or observations of your doctoral research?

The key findings of my doctoral research center around the understanding that microRNAs have a broad impact on entire pathways rather than individual targets, emphasizing the importance of considering their cumulative effects. This underscores the necessity of integrating omics-integrative approaches when studying non-coding RNAs (ncRNAs).

In terms of implementation, my research employs a multidisciplinary approach, combining advanced molecular techniques, single-cell and spatial transcriptomics, clinical investigations, and in vivo studies. This holistic approach promises to provide concrete insights into the involvement of ncRNAs in neurodegenerative diseases, addressing the complex interplay of feedback loops and regulatory molecules. 

What sets my research apart is its focus on unraveling the intricate regulatory networks involved in neurodegenerative diseases, particularly in the challenging context of brain pathologies. By elucidating these mechanisms, my research aims to guide the development of therapeutic strategies tailored to account for the complexity of these networks, potentially overcoming current obstacles in treatment.

How can the results of your doctoral research be utilised in practice?

Moreover, the implementation of RNA therapies for genetic diseases and vaccines underscores their transformative potential in healthcare. The minimally invasive administration and rapid adaptability of RNA therapies offer promise for tailored interventions in various conditions, including neurodegenerative diseases. Thus, my research findings not only contribute to scientific understanding but also hold potential for translating molecular insights into effective clinical applications, advancing the development of therapies for neurodegenerative disorders. This aspect of my research is both valuable and interesting for both the scientific community and the general public, as it offers hope for improved treatments for devastating diseases affecting millions worldwide.

What are the key research methods and materials used in your doctoral research?

In this thesis, the study of miR-7a-5p serves as fil rouge illustrating the multifaceted regulatory landscape of miRNAs during stress which encompasses transcriptional, post-transcriptional, spatial, temporal, and cell specific regulation. The process involved employing cutting-edge technologies and advanced molecular techniques to unravel the complex regulatory networks of ncRNAs.

Key research methods and materials utilized in my doctoral research included:

1. Cellular and animal models: I utilized in vitro neuronal models to study the post-transcriptional regulation of ncRNAs, particularly miR-7, under stress conditions such as oxygen-glucose deprivation (OGD). Additionally, I employed in vivo rodent models of neurodegenerative diseases to investigate the role of ncRNAs in disease pathogenesis.

2. Single-cell spatial transcriptomics: To understand the heterogeneity of cellular states and the impact of ncRNAs, I employed single-cell RNA spatial transcriptomic techniques, providing insights into cellular responses to stress and disease.

3. Functional cell separation techniques: I utilized fluorescence-activated cell sorting (FACS) to isolate specific cell populations, such as microglia, before conducting transcriptomic analysis. This approach enabled a deeper understanding of the role of ncRNAs in disease-relevant cell types.

4. Extracellular vesicle (EV) analysis: I investigated the role of EV-loaded miRNAs in intercellular communication and disease progression. By considering the intra- and extra-cellular localization of ncRNAs, I explored their diverse roles in various cellular types and their potential as biomarkers for disease.

5. Database generation and annotation: As part of my research, I generated a database to annotate circulating ncRNAs, highlighting their variable roles in different disease contexts. This database aimed to provide valuable information on ncRNA detection methods and limitations to inform future research endeavors.

Overall, my doctoral research employed a multidisciplinary approach, combining cellular and animal models, single-cell transcriptomics, functional cell separation techniques, and database generation to unravel the complex roles of ncRNAs in stress responses and neurodegenerative diseases. This comprehensive approach aimed to contribute to our understanding of ncRNA-mediated regulatory networks and their potential implications for disease diagnosis and treatment.

The doctoral dissertation of Flavia Scoyni, MSc, entitled Unlocking the potential of non-coding RNAs in regulating neurodegeneration – a glimpse into Alzheimer’s disease and ischemic stroke pathophysiology will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Professor Alessandro Rosa of the Sapienza University of Rome, and the Custos will be Professor Tarja Malm of the University of Eastern Finland.

Doctoral defence