Ricerc@Sapienza

Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating
mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In
the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization
and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in
a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin

Constitutive heterochromatin represents a significant portion of eukaryotic genomes,
but its functions still need to be elucidated. Even in the most updated genetics
and molecular biology textbooks, constitutive heterochromatin is portrayed
mainly as the ‘silent’ component of eukaryotic genomes. However, there may be
more complexity to the relationship between heterochromatin and gene expression.
In the fruit fly Drosophila melanogaster, a model for heterochromatin studies,
about one-third of the genome is heterochromatic and is concentrated in the

Centromeres are epigenetically determined chromatin structures that specify the assembly site of the kinetochore, the multiprotein machinery that binds microtubules and mediates chromosome segregation during mitosis and meiosis. The centromeric protein A (CENP-A) and its Drosophila orthologue centromere identifier (Cid) are H3 histone variants that replace the canonical H3 histone in centromeric nucleosomes of eukaryotes. CENP-A/Cid is required for recruitment of other centromere and kinetochore proteins and its deficiency disrupts chromosome segregation.

A very important open question in stem cells regulation is how the fine balance between GSCs self-renewal and differentiation is orchestrated at the molecular level. In the past several years much progress has been made in understanding the molecular mechanisms underlying intrinsic and extrinsic controls of GSC regulation but the complex gene regulatory networks that regulate stem cell behavior are only partially understood. HP1 is a dynamic epigenetic determinant mainly involved in heterochromatin formation, epigenetic gene silencing and telomere maintenance.

Deep underground laboratories (DULs) were originally created to host particle, astroparticle or nuclear physics experiments requiring a low-background environment with vastly reduced levels of cosmic-ray particle interference. More recently, the range of science projects requiring an underground experiment site has greatly expanded, thus leading to the recognition of DULs as truly multidisciplinary science sites that host important studies in several fields, including geology, geophysics, climate and environmental sciences, technology/instrumentation development and biology.

Recent work has implicated the actin cytoskeleton in tissue size control and tumourigenesis, but how changes in actin dynamics contribute to hyperplastic growth is still unclear. Overexpression of Pico, the only Drosophila Mig-10/RIAM/Lamellipodin adapter protein family member, has been linked to tissue overgrowth via its effect on the myocardin-related transcription factor (Mrtf), an F-actin sensor capable of activating serum response factor (SRF). Transcriptional changes induced by acute Mrtf/SRF signalling have been largely linked to actin biosynthesis and cytoskeletal regulation.

SMN (Survival Motor Neuron) deficiency is the predominant cause of spinal muscular atrophy (SMA), a severe neurodegenerative disorder that can lead to progressive paralysis and death. Although SMN is required in every cell for proper RNA metabolism, the reason why its loss is especially critical in the motor system is still unclear. SMA genetic models have been employed to identify several modifiers that can ameliorate the deficits induced by SMN depletion.