Biology subjects

Mornico, D.

Publications and source records attributed to Mornico, D..

4 recordsLinked to original sources

bioRxiv2025

Cell competition overcomes host tissue resistance to unleash tumour growth in a Drosophila brain cancer model

Primary tumours of the central nervous system are extremely aggressive and often incurable. While tumours are known to interact with their microenvironment, how the interplay between tumour cells and the host tissue controls tumour progression remains elusive. We addressed this question in a Drosophila model of cancer stem cell-driven tumour which originates during development and grows extensively within a network of cortex glia cells (CG) through adulthood. We found that tumour growth induces progressive remodeling of the CG network and leads to CG apoptosis through cancer stem cell-driven competition, a process which in turn unleashes tumour growth. Notably, preventing CG death reduces tumour growth, revealing a resistance capacity within the CG. Transcriptional profiling of CG cells at different stages revealed a biphasic response, featuring an early specific signature followed by a later collapse of essential cellular functions and pathways, including the conserved JNK pathway. JNK signalling in CG normally plays a neuroprotective role and initially hinders tumour progression, providing resistance. However, its subsequent downregulation eventually brings the collapse of the host tissue, ultimately curbing tumour growth. This study uncovers a dynamic and complex interplay between host tissue resistance and tumour-driven competition, which shapes tumour progression.

cell biology↗

bioRxiv2024

Global evolutionary patterns of Yersinia pestis and its spread into Africa

The zoonotic pathogen Yersinia pestis, the etiologic agent of plague, has caused three major pandemics and diversified in different lineages currently established in endemic areas worldwide1-3. However, some regions like continental Africa have been poorly covered within the global diversity and epidemiological history of this pathogen2,4-6. Here, we report the whole-genome sequences of 1,124 Y. pestis isolates collected from endemic areas worldwide over 116 years, nearly doubling the available genomic data for the species. By integrating population genomics and historical research, we retrace the introduction of multiple Y. pestis lineages into continental Africa, revealing the diversity of the 1.ANT lineage, its historical emergence and its spread to and within Africa since the late 17th century. We identify key mechanisms of genome evolution, including signatures of adaptive evolution present in virulence and biofilm-related genes such as RovA, a master virulence regulator, which likely play a role in the pathogens adaptation and endemic persistence. Additionally, our findings reveal an increased trajectory of genome degradation and expansion of IS elements in different lineages. This trend appears especially pronounced in 1.ANT genomes, promoting the remarkable genomic variation within this lineage. Taken together, our findings shed light on the introduction and evolutionary history of plague in Africa and provide a comprehensive framework for understanding the global diversity and genome evolution of Y. pestis, revealing potential factors contributing to its long-term adaptation in endemic areas.

microbiology↗

bioRxiv2022

Chromosomal position of ribosomal protein genes impacts long term evolution of Vibrio cholerae.

It is unclear how gene order within the chromosome influences bacterial evolution. The genomic location of genes encoding the flow of genetic information is biased towards the replication origin (oriC) in fast-growing bacteria. To study the role of chromosomal location on cell physiology we relocated the S10-spec- locus (S10), harboring half of ribosomal protein genes, to different chromosomal positions in the fast-growing pathogen V. cholerae. We found that growth rate, fitness and infectivity inversely correlated the distance between S10 and oriC. To gain insight into the evolutionary effect of ribosomal protein genomic position, we evolved strains bearing S10 at its current oriC-proximal location or derivatives where the locus far from it, at the chromosomal termini. All populations increased their growth rate along the experiment regardless S10 genomic location. However, the growth rate advantage of an oriC-proximal location persisted along experimental evolution indicating that suppressor mutations cannot compensate S10 genomic position. An increment in biofilm forming capacity was another common trait observed along the experiment. Deep sequencing of populations showed on average 1 mutation fixed each 100 generations, mainly at genes linked to flagellum biosynthesis regulation, lipopolysaccharide synthesis, chemotaxis, biofilm and quorum sensing. We selected fast-growing clones displaying a [~]10% growth rate increment. We found that they harbored inactivating mutations at, among other sites, the flagellum master regulators flrAB. The introduction of these mutations into naive V. cholerae strains resulted in a [~]10% increase of growth rate. Our study therefore demonstrates that the location of ribosomal protein genes conditions the evolutionary trajectory of growth rate in the long term. While genomic content is highly plastic in prokaryotes, gene order is an underestimated factor that conditions cellular physiology and lineage evolution. The lack of suppression enables artificial gene relocation for genetic circuit reprogramming.

microbiology↗

bioRxiv2018

The molecular logic of Nanog-induced self-renewal

Transcription factor networks, together with histone modifications and signalling pathways, underlie the establishment and maintenance of gene regulatory architectures associated with the molecular identity of each cell type. However, how master transcription factors individually impact the epigenomic landscape and orchestrate the behaviour of regulatory networks under different environmental constraints is only very partially understood. Here, we show that the transcription factor Nanog deploys multiple distinct mechanisms to enhance embryonic stem cell self-renewal. In the presence of LIF, which fosters self-renewal, Nanog rewires the pluripotency network by promoting chromatin accessibility and binding of other pluripotency factors to thousands of enhancers. In the absence of LIF, Nanog blocks differentiation by sustaining H3K27me3, a repressive histone mark, at developmental regulators. Among those, we show that the repression of Otx2 plays a preponderant role. Our results underscore the versatility of master transcription factors, such as Nanog, to globally influence gene regulation during developmental processes.

genomics↗