PhD thesis - genetic and cell biology

Human Orthologous Tumours in Dogs : characterization of natural models for genetics and therapies

Socio-economic and scientific context

Since the domestication of wolves (-15 à - 40 000 years), humans have created a hudge number of dog breeds (>400), for highly diverse purposes. Thus, each breed is considered as a genetic isolate, in which specific diseases segregates. Its close proximity to human lives makes the dog  a very relevant model to identify the genetic bases  of homologous cancers between dogs and humans. In addition, these 2 species share the same environnement, allowing the analysis of gene-environnement interactions. Dogs thus constitute an promising resource of pre-clinical models. Faced to the growing interest of personalized medicine and the developpement of numerous targeted therapies, screening the therapeutic efficacy of targeted drugs now becomes a challenge. We thus propose canine cancers to help human medicine to select the most relevant therapies of therapy combinations in human and canine oncology. 

Hypotheses et questions asked

Numerous dog breeds are affected by different types of human othologous cancers. Interstingly, many canine cancers are breed specific, allowing to hypothesize genetic susceptibilities that have been fixed in certain breeds. In addition, our results on the identification of somatic mutations and transciptome analyses  show that identical mechanisms are involved, with the same genes, even the same mutation hotspots in orthologous cancers.

The team have developped the tools to characterize such spontaneous cancer models and to compare them with their human counterparts on the clinical, histological, genetical and cellular aspects ; from the identification of genetic alterations to their therapeutic screening, making these models more and more attractive.

We propose to use NGS tools (New Sequencing Generation) and the developpement of canine cell lines, tools well known in the team, to caracterise  comparative oncology based canine models.

Main stages of the thesis and approach

Several types of human hematopoietic cancers are also diagnosed in dogs and are naturally occuring in the course of their lives; lymphomas et histiocytic sarcomas for example are strongly breed specific and are already well studied in the team.

The PhD project will aim to (i) continue their caracterization at the molecular level (chromosomal alterations and genetic predispositions as well as somatic alterations, fusion genes, alternative transcripts, differential expression …) and to compare them to their human counterparts (ii) develop primary cultures and cell lines of those canine cancers to test and develop new therapeutic options for the benefit of human and veterinary medicine.

Methodological and technical approaches proposed

The team has developped a network to collect samples via the cani-DNA national Biobank as well as molecular and bioinformatics tools dedicated to the canine genome.

The first step will be to select relevant samples for genetic analyses and to pursue the collection.

The student will then use the NGS sequencing technologies on the germinal DNA to identify genetic prédispositions and on the somatic DNA (from affected tissus with controls), to identify somatic alterations. The second step will consist in the cell culture of the collected tumours, to finally characterize and fonctionnaly validate the genetic alterations and to test the therapeutique efficacy of several dedicated drugs.

Scientific and technical expertise required by the candidate

  • Solid knowledge in biology and molecular genetics
  • Good knowledge in oncology
  • If possible, expertise on cell culture
  • A nice  motivation for medical research

To apply or for informal enquiries

Please send to Dr Catherine ANDRÉ  and Benoît HÉDAN the information below (preferentially by email and PDF):

  • A Curriculum Vitae (CV)
  • A cover letter detailing your motivation and skills to take over the project
  • The names of two referees

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