Genetics, Biobanking and Molecular Biology
16:05 - 17:25 | Meeting Room 101 (Level 1)
Chair: Prof. Stephanie Bezzina Wettinger
Dr Kay Polidano
Department of Sociology, Faculty of Arts
Data sharing is a central practice in biobanking, enabling the pooling and reuse of biological samples and health-related data to advance scientific research. Such data are typically shared with approved academic, clinical, and public health researchers through controlled access arrangements. Existing research highlights that public trust in the ethical governance and transparency of data sharing practices is essential to the sustainability of biobanking initiatives. However, empirical studies examining public trust and data sharing in biobanking remain largely focused on large national contexts, offering limited insight into how these practices are experienced within small, socially interconnected societies like Malta.
This paper presents emerging findings from a mixed-methods study conducted with participants in Malta’s national biobank, exploring preferences, concerns, and expectations regarding data sharing practices. Data collection comprised an online survey and qualitative interviews. Quantitative data capture patterns of trust, consent preferences, and perceived risks associated with data sharing, while qualitative findings illuminate how these attitudes are shaped by social relations, cultural norms, and concerns around anonymity in a small-state setting. This enables a contextualised understanding of how ethical principles surrounding data sharing are interpreted and enacted in practice.
The findings highlight how trust, consent, and data-sharing practices are negotiated under conditions of social proximity in a small nation-state. They offer context-sensitive insights that may be relevant to other small or culturally distinct populations and contribute to broader debates on ethical biobank governance.
Dr Alessandro Balestrucci
Department of Applied Biomedical Science, Faculty of Health Sciences | Centre for Molecular Medicine and Biobanking
This project was initiated to replace file-based VCF management with an optimised relational database approach for efficient storage and retrieval of genomic variants.
The solution has since evolved to natively integrate diverse types of omics data, aiming to overcome the fragmentation typical of multi-modal research. Its architectural core is a star schema that places biological samples at the centre, structurally and scalably linking heterogeneous datasets (such as genomic, transcriptomic, and, prospectively, proteomic and metabolomic data) all pertaining to the same subjects.
In addition to genetic data (SNPs, annotations, genotypes), modules for transcriptomics data have already been implemented, demonstrating the system's expandability. To evaluate its effectiveness, realistic use cases were defined and comparative benchmarks against alternative approaches were conducted. Results show superior or competitive data retrieval performance across many scenarios, confirming that a sample-centric relational approach not only enables full multi-omics linkability but can also ensure operational efficiency. The system thus presents itself as a unified, performant, and forward-looking infrastructure for integrated biomedical research.
Ms Amy Marie Vella
Department of Applied Biomedical Science, Faculty of Health Sciences
The RNA export mediator GLE1 is a gene located on chromosome 9 that codes for two structurally similar protein isoforms, GLE1A and GLE1B, that differ at their COOH terminal domains: GLE1B is 43 amino acids long, whereas GLE1A spans only 4 amino acids. Pathogenic variants in GLE1, both compound heterozygous and homozygous, are responsible for two autosomal recessive disorders: Lethal Congenital Contracture Syndrome 1 (LCCS1) and Congenital Arthrogryposis with Anterior Horn Cell Disease (CAAHD). LCCS1 is invariably fatal in the foetal period while individuals with CAAHD may survive into childhood albeit with significant disability. Survivability in CAAHD depends on both the location of the pathogenic variant and the availability of early medical intervention.
A local founder variant, the GLE1 p.S693F was identified in the homozygous state in an affected child. The variant is located at the end of exon 16, thus only affecting the GLE1B isoform. The child has now survived beyond his first decade of life, raising the question of whether having only one malfunctioning isoform results in a less severe presentation of the condition.
Previous studies have demonstrated that concurrent knockdown of both gle1 isoforms in zebrafish results in a phenotype that closely resembles LCCS1. However, the phenotypic consequences of retaining one functional isoform have not yet been explored. To investigate this, zebrafish (Danio rerio) was used as a model organism to knock down only one isoform, the gle1b. Splice blocking morpholinos, MO14 and MO15, were designed to specifically target and knockdown the long gle1b isoform. In parallel, fish with complete gle1 knockdown were also examined to determine whether selective isoform knockdown resulted in a milder phenotype.
Morphological analysis showed that gle1b knockdown embryos developed normally with only mild and transient morphological abnormalities, contrary to the severe morphological abnormalities observed in fish with complete gle1 knockdown. Behavioural analysis further demonstrated that although gle1b knockdown fish were responsive to stimuli, their motor activity was reduced compared to wildtype controls. Still, their activity levels were higher than those observed in fish with complete gle1 knockdown, which showed minimal to no response. Additionally, gle1b knockdown resulted in craniofacial cartilage defects, characterised by a shorter and narrower cranium. Cell death analysis revealed increased apoptosis in the central nervous system, head, and heart, although to a lesser extent than in complete gle1 knockdown embryos.
Altogether, these findings support the hypothesis that having a single, functional GLE1 isoform results in a milder phenotype and increased survival. This is consistent with the clinical presentation observed in the Maltese patient and provides further insight into the isoform-specific contribution of GLE1 to disease severity.
Prof. Melissa M. Formosa
Department of Applied Biomedical Science, Faculty of Health Sciences
Introduction: Osteosarcopenia, the concurrent decline of bone (osteoporosis) and muscle (sarcopenia), constitutes a major global health burden, significantly increasing the risk of falls, fractures, and institutionalisation. The STRONG study (R&I:2024-007L) aims to identify and validate novel drug targets from a library of natural products (NPs) to improve both bone and muscle health. The overarching goal is to discover potential supplements or therapeutics with good compliance and minimal side effects that can promote active ageing.
Methodology: Toxicity testing and drug exposure were conducted for several NPs using a testing pipeline developed in-house. Gross morphological assessment was carried out daily to assess drug toxicity, whereas neurotoxicity was assessed using a zebrafish tracker (DanioVision) at 5dpf and 7dpf. Bone mineralisation was assessed at 7dpf using the combined alcian blue and alizarin red staining of the opercula normalised to head size. Mineralisation was quantified using Fiji ImageJ, and statistical analysis was carried out using GraphPad Prism 10.3.1.
Results: No gross morphological malformations or neurotoxicity were observed for any of the tested NPs till 7dpf. Zebrafish larvae at 7dpf displayed significant increases in cranial mineralisation following exposure to NP-1 (p<0.0001), NP-2 (p≤0.01) and NP-3 (p≤0.01) compared to untreated WT controls, highlighting their osteoanabolic potential.
Conclusions: Findings suggest that some NPs could have osteogenic potential. This research pipeline is expected to identify lead compounds for conditions like osteosarcopenia. Furthermore, the study aims to widen the knowledge of the genetic factors and signalling pathways governing bone and muscle pathophysiology, thereby accelerating therapeutic discovery.
Prof. Pierre Schembri-Wismayer
Department of Anatomy, Faculty of Medicine and Surgery
In 2006, Prof. Shinya Yamanaka published a seminal paper, the research of which was awarded both the Nobel Prize and the Breakthrough Prize. This research allowed a fully differentiated adult cell, such as a skin cell (or later, a blood cell), to be modified into a pluripotent stem cell capable of becoming all other cell types in the body, including liver cells, bone cells, and nerve cells. The process initially required genetic modification but is now performed without permanent modification, using certain viruses, mRNA, non-integrating DNA, or proteins. All of these methods are, however, costly and also of low efficiency. A couple of publications used complex small molecules, which again are somewhat expensive, have considerable side effects and also resulted in low efficiency.
UM’s CATSCI lab has been studying for a while methods of producing these pluripotent stem cells, previously from cord blood and now from peripheral blood, such that they would be available at a very reasonable cost to everyone. The drugs used in this conversion process, which appears much more efficient than that of Yamanaka (and derivatives), use nutritional agents and commonly used drugs already on the market, in particular combinations and orders. Ongoing research is attempting to further enhance efficiency and process robustness to develop a commercial product for medical use.
Prof. Lee Presley Gary, Jr.
Department of Public Health, Faculty of Medicine and Surgery
Our project aims to prepare and document an impact spectrum of Legionella bacteria, designed to assess public health awareness and readiness in Malta, as well as the impact on residents’ well-being from exposure. To date, our initial finding is a surprising and unexpected dearth of peer-published research on the potential health threats and hazards, latent and emerging, posed by rogue Legionella sources in Malta. Our ongoing research project began with a scoping exercise among university faculty, staff, and community health officials to define the structure and content of the proposed impact spectrum. Next, we expanded to designing and launching a systematic review of major literature sources to construct and conduct, ultimately, a meta-analysis of suspect health threats and hazards. Also, we have obtained access to 10 years of summary reports on infectious diseases in Malta, while systematically preparing for a SPSS comparative analysis of Legionella diseases and other major pathogens in Malta, perhaps expanding to other Mediterranean countries. Our commitment remains that new, unique or novel information generated by this project will be shared with relevant stakeholders to update, where appropriate, laws and regulations for the prevention and control of Legionella bacteria when unleashed in Malta.