The 5xmille donation

Thanks to the support of the 5xmille, my group has developed a project aimed at studying the role of brain inflammation in Alzheimer's Disease. This neurodegenerative disease is the most common form of dementia in the elderly and remains incurable to this day. Recent years have seen the emergence of neuro-inflammation as a factor in the onset and progression of Alzheimer's, but there is still much work to be done to fully understand these mechanisms and translate them into treatments. Our project hypothesizes that an increase in neuro-inflammation may represent a crucial and initial step in this disease, and that addressing this process early on may delay or alleviate the onset of symptoms. In the laboratory, we use the fruit fly, Drosophila melanogaster, as a model to study these processes. Thanks to our "Alzheimer's flies," we can monitor the onset of specific symptoms while simultaneously assessing brain inflammation. The project is still in its early stages but is already yielding its first interesting results, and we hope, within a couple of years, to have a precise understanding of the timing of inflammation onset and its effects on neurodegeneration.

The 5xmille has been a fundamental support in allowing my newly formed group to advance this project. I believe it is very important for each of us, in our own small way, to contribute to the progress of biomedical scientific research with a small gesture, such as donating our 5xMille. Indeed, the choices we make today will bear fruit in the medical and health advancements we will see in the coming years, which will bring improvements for everyone. Choosing to donate it to SISSA means supporting high-quality scientific research projects, carried out by qualified scientists who are passionate about their work, in a top-level environment.

Xia-Gibbs Syndrome (XIGIS) is a rare genetic disorder where a gene called AHDC1 is damaged. It's a neurodevelopmental disorder, which means that, when AHDC1 is damaged, during embryo development, various problems in the brain arise that cause intellectual, motor, and physical disabilities. The 5x1000 funds donated to SISSA in 2021 were used in 2022 to support an ongoing research project in the Computational Genomics laboratory I coordinate to develop resources and fine-tune experiments that allow the study of the molecular functions of AHDC1. This is important because, although the gene is known to be causative of XIGIS, little to nothing is known about its functions in the cell. The resources and experiments that it was possible to produce in 2022 also thanks to the use of 5x1000 funds were: Design and production of an antibody capable of recognizing the protein encoded by the AHDC1 gene. With this reagent, we can identify, visualize, and study the protein produced by the AHDC1 gene in cell extracts and under the microscope. Execution of real-time qPCR experiments. With these experiments, we can validate the transcription of genes that are responsive to the perturbation of AHDC1 resulting from transcriptome sequencing analyses previously carried out within the project. Design and preparation of samples for ChIP-seq experiments on HP1 and AHDC1. With these experiments, we can identify the genomic regions bound by HP1 and AHDC1 in response to the perturbation of AHDC1. These are crucial experiments because they help to understand what happens to chromatin organization in response to perturbations of AHDC1 and thus to identify possible regulatory pathways that may be interesting molecular targets in experimentation. Acquisition of reagents and fine-tuning of cell lines derived from XIGIS patients. We have started working on cell lines derived from patients' blood and are growing them in the laboratory. On these, we can perform validations of the expression of genes responsive to perturbations of AHDC1 and use them as cellular models for future experiments. The project began in 2019. To date, it is still ongoing. The results produced so far have allowed us to understand which are some of the genes responsive to perturbations of AHDC1 and which are the possible targets to focus future research on both to understand the molecular mechanisms in which AHDC1 participates and to target in clinical experimentation to try to improve the quality of life for patients and their families.

SISSA is a place where people with an extremely diverse and heterogeneous background conduct research. One of the features that I like most is precisely that, despite our heterogeneity, we often manage to talk to each other and, driven also and especially by the School itself, we try to integrate our knowledge and scientific interests into collaborative projects that greatly extend the possibilities of a single laboratory and/or a single topic. We often manage to address a scientific question from different points of view, and this leads us more easily and more quickly to produce results useful to the community. Therefore, the 5xmille to SISSA is for 360-degree research.