The Neurogenomics group coordinated by Gustincich studies the molecular basis of neurodegenerative diseases. The genome and transcriptome of neurons are analyzed to unveil features and pathways involved in cellular susceptiblility to brain diseases such as Parkinson’s disease, Alzheimer's disease.
Blood transcriptomics aims to identify a gene signature for PD diagnosis. Special emphasis is dedicated to the role of long non-coding RNAs (lncRNAs) and repetitive elements.
Parkinson's disease (PD) is a slow, progressive, degenerative movement disorder of the central nervous system. The neuropathological hallmark in post−mortem brains is the selective degeneration of specific subsets of mesencephalic dopaminergic cells and the presence of cytoplasmic inclusions called Lewy bodies. Although most PD cases are sporadic, families with genetic mutations have been found. The etiology and the initial molecular events of sporadic PD remain unclear. No pre-symptomatic diagnosis and pharmacological treatments are currently available.
In the last years we have been at a very exciting and crucial crossroad in the post-genomic era. Results from the ENCODE project have being published, increasing enormously our description of the molecular constituents of cells. Meantime, the fifth FANTOM project, organized by RIKEN, Japan is unveiling transcriptional regulatory networks at an unprecedented scale.
These works are demonstrating that the majority of the mammalian genome is transcribed. This generates a vast repertoire of transcripts that includes long non-coding RNA (lncRNA) and repetitive sequences, such as SINEs (short interspersed nuclear elements) and LINEs (long interspersed nuclear elements). Repeat elements can form independent transcriptional units or be embedded in mRNA or lncRNAs. A large percentage of lncRNAs are nuclear-enriched with unknown function. Surprisingly, the large majority of genes share their genomic region with another gene on the opposite filament forming Sense/Antisense (S/AS) pairs. Furthermore, transcription and retrotransposition of LINEs and SINEs occur during neurogenesis creating somatic differences in genomic DNA sequences of neuronal cells.
The role of lncRNAs, antisense transcription and repetitive elements in brain function and neurodegenerative diseases remain largely unknown.
The laboratory of Neurogenomics is focusing on the following projects:
1. Blood transcriptomics of PD.
2. The transcriptional landscape of dopaminergic cells.
3. The function of Hemoglobin in dopaminergic cells.
4. SINEUPS: a new functional class of long non-coding RNAs.
5. RNA therapeutics.
6. The role of repetitive elements in brain function.
