Daphne Cabianca: Environment and Nuclear Organization

In recent years, it has emerged that epigenetic modifications link the environment and the genome. A striking example is the metabolic state of the cell. In fact, enzymes that modify chromatin do so using metabolic intermediates as cofactors, therefore the nutritional state of an organism can impact on its epigenome. Despite such a tight connection, how cells and organisms respond to and “protect” their epigenomes in face of fluctuations of metabolites remain largely unknown.

Chromatin exists into two main flavors: transcriptionally active euchromatin and repressed heterochromatin. These are marked by different histone modifications and occupy distinct nuclear locations, generating a functional compartmentalization of the genome that is conserved from yeast to man. Our group aims at understanding how environmental stress, particularly nutrients availability, affects the state, spatial compartmentalization and function of chromatin within an intact developing organism, namely the roundworm C. elegans

About the model system C. elegans

Since the 1960s, the nematode Caenorhabditis elegans has been used as model organism to investigate numerous biological processes.

The nematode develops rapidly: it progresses from embryo through four larval stages and to adult in only 3 days at 20 °C.  With its 959 somatic cells, C. elegans combines the complexity of a multicellular organism with a relatively simple physiology and is ideal to study cellular differentiation and various developmental processes.

C. elegans is genetically manipulatable and suited for large scale RNAi screens. This, combined to the fact that they are transparent throughout development, renders the worms great for live microscopy-based studies of fluorescently tagged proteins and/or chromatin reporters. With their short life cycle and controlled genetics, worms are ideal to study epigenetic memory not only through different stages of development, but also across generations. In recent years, C. elegans has emerged as model organism to study metabolism. In fact, its highly controlled diet that solely consists of bacteria, favors research that involves nutrition control. C. elegans is a unique system where to investigate the effects of diet on chromatin organization within intact tissues of a whole organism. Given the high degree of conservation in most chromatin and metabolic pathways with mammals, discoveries in C. elegans are relevant to human biology

Our research approach

Our approach aims at identifying the molecular players involved in the chromatin organization response to stress to then be able to test for functionality by means of genetic manipulations.

We combine a series of cutting-edge techniques that allow us to address our questions from different angles. Among others we utilize:

  • Spinning disc confocal live microscopy to monitor protein and chromatin localization at the subnuclear scale
  • Genetic editing via CRISPR-Cas9
  • RNAi screens
  • ChIP, DamID and ATACseq to probe for chromatin state and compartmentalization
  • RNAseq for gene expression
  • Organismal assays like stress survival

About Daphne Cabianca

Daphne is Italian and did her undergraduate studies in Pavia, Italy, where she worked on alternative pre-mRNA splicing regulation. She took her PhD at the San Raffaele Scientific Institute in Milan working on the chromatin alterations occurring in Facioscapulohumeral Muscular Dystrophy (FSHD), a disease caused by a reduction in the copy-number of a macrosatellite tandem repeat. Her study contributed to the understanding of how repetitive DNA and long ncRNAs can regulate transcription with consequences for human pathology (Cabianca et al., Cell 2012).

In 2013, she moved to Basel, Switzerland joining Susan Gasser’s group as a postdoctoral fellow. Here, she took the challenge of completely changing model systems, using the nematode C. elegans to study chromatin spatial organization in cell differentiation. She pioneered a high resolution, microscopy-based RNAi screen looking at subnuclear structure in larvae. Daphne’s work revealed that perturbation of the active chromatin compartment impairs the spatial sequestration and transcriptional silencing of heterochromatin at the nuclear envelope, unravelling a novel mechanism that implicates cross-talk with euchromatic factors including CBP/p300 acetyltransferase (Cabianca et al., Nature 2019). Since April 2020, she joined the Institute of Functional Epigenetics of HMGU as a junior group leader.

For her publication record go here.