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A study model for Ewing sarcoma in Drosophila.


Ewing sarcoma is the second most frequent bone tumour in children, adolescents, and young adults. There is no specific treatment for this disease and current management is still limited to surgery, radiotherapy, and chemotherapy. The long-term survival of patients with metastatic or relapsed Ewing sarcoma is very low.

Ewing sarcoma is caused by a single oncogene that results from the fusion of two genes. Although a variety of genes may be involved, EWSR1 and FLI1 and the resulting cancer-driving oncogene, known as EWS-FLI, are found to be responsible in the majority of patients. Unlike most other types of cancer, all attempts to develop experimental animal models of Ewing sarcoma in mice (expressing the EWS-FLI oncogene) have failed.

Prompted by the need for a genetically tractable model that could be used to study the disease, researchers led by Dr. Cayetano González, ICREA research professor at IRB Barcelona, and Dr. Jaume Mora, scientific director at the IRSJD Pediatric Cancer Center Barcelona (PCCB), have engineered Drosophila transgenic strains that express a mutant variant of the human oncogene called EWS-FLIFS. Remarkably, they have found that expression of the human EWS-FLIFS protein in certain types of Drosophila cells triggers the same oncogenic pathways known to account for EWS-FLI oncogenic activity in human patients.

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"Illuminati": a new gene inactivation mechanism that influences development and is related to disease

Defects in the various cellular mechanisms that prevent mutations and chromosomal abnormalities can lead to genomic instability, which is associated with a wide variety of diseases, such as ataxia telangiectasia, xeroderma pigmentosum, and cancer.

Our laboratory uses Drosophila as an experimental model to understand the causes and consequences of GI. In collaboration with the laboratory of Dr. Renata Basto (Curie Institute, Paris) we have developed a tool to investigate genomic instability. This tool consists in transgenic flies carrying reporters engineered such that a fluorescent signal is turned on only in cells in which genome integrity is compromised. The key to this reporter system is a protein called Gal80. Mutation in the gene that encodes this protein or loss of the chromosome carrying this gene act as molecular triggers that lead to the expression of a fluorescent protein.

These are highly sensitive reporters that can detect cases of GI affecting a single cell in the entire organism. We are currently taking advantage of these reporters to investigate different issues regarding genetic instability including GI contribution to malignant growth, sex-biased differences, and others.

Understanding the assembly of neuronal cilia, the structures that sense chemicals and mechanical forces (thus allowing for smelling, hearing, and many other essential functions). 2


This study focuses on a type of neuronal cilia, the structures that by sensing chemicals and mechanical forces allow for smelling, hearing, and many other essential functions. 

Many cells in our bodies present a small structure that looks like, and as a matter of fact works as an antenna, conveying to the cell information on the extracellular environment. They are called cilia (plural) or cilium (singular). Ciliated cells play essential functions in the human body. Thus, for instance, the monitoring of fluid flow in the kidney, the detection of hormones in the brain, or the senses of hearing and smell depend on specialised neurons equipped with chemo-sensory or mechano-sensory cilia. Moreover, besides sensing, beating cilia keep fluids in motion in many parts of our bodies and are critical for human health. 

A cilium can be regarded as a long and thin protrusion of the cell membrane that contains microtubules. Ciliary microtubules are arranged in a typical radial symmetry that is conserved through evolution and is templated by a small organelle that sits at the base of the cilium, known as basal body. Most animal cells contain two basal body-like structures (centrioles), but only one of them can actually work as basal body. In human cells, this is always the centriole that is said to be the "mother" (red dot in this image) because it was assembled earlier than the other, called the "daughter" centriole (green dot in this image).

A method to transplant tumours in flies.The revival of an old, but powerful technique.


A method to transplant tissue from donor larvae to adult fly hosts, which can be used to study many biological processes including malignant growth.

In 2002, when facing a major technical problem, the Gonzalez  group took advantage of two of the many benefits of using the vinegar fly, Drosophila melanogaster, for scientific research: the variety of methods and tools generated over more than a century of work with this fascinating organism, and the culture of sharing  that is deeply rooted in the Drosophila research community.

The problem was to carry out in flies an assay that is standard to investigate cancer in mammals, including humans, which consist in transplanting the tumour mass to mice; implanted healthy tissues cannot overgrow, but malignant tumours grow without limit and kill the host. The solution seemed simple because, indeed, among the battery of methods developed by fly researchers there is a technique for tissue transplantation. But there still was a problem.

Key protein in sperm tail assembly identified.

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The study, published in The Journal of Cell Biology, focuses on the development of the sperm tail, the structure that enables sperm cells to swim and is therefore critical for male fertility.

In flies, as in humans, the sperm cell (spermatozoon) is made of the cell body proper, which is also referred to as the sperm “head”, and the flagellum. The flagellum, also known as the sperm “tail”, is a slender lash-like appendage that protrudes from the cell body. It is by beating their tails that sperm cells can swim to reach and fertilise the female reproductive cell (oocyte). A bundle of microtubules that span the entire length of the tail is critical for flagellar beating. These microtubules are arranged in a characteristic radial symmetry that is conserved through evolution and is templated by a small organelle that sits at the base of the flagellum, known as basal body.

Using the vinegar fly Drosophila melanogaster as an animal model to investigate how the sperm tail develops we found that CENTROBIN plays a critical role in the assembly of a subset of microtubules within basal bodies. In the absence of CENTROBIN, basal bodies lack these microtubules and so do the tails that they template that are not motile. Consequently, CENTROBIN mutant males are sterile.

How similar are fruit fly and human cancers? New evidence for genome instability in fly tumors suggests key similarities—and differences—from human disease processes.


Read ARTICLE SUMARY published in Genetics Society of America's blog, 

PUBLISHED IN  Fabrizio Rossi, Camille Stephan-Otto Attolini, Jose Luis Mosquera, Cayetano Gonzalez (2018). Drosophila Larval Brain Neoplasms Present Tumour-Type Dependent Genome Instability G3: Genes|Genomes|Genetics 2018 8: 1205-1214;

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(C) Gonzalez 2022