Identifying new targets to inhibit brat tumour growth in Drosophila melanogaster through combined transcriptomics and functional genome-wide analysis

[eng] I have used the brain tumours that originate in Drosophila larvae upon depletion of the brain tumor (brat) gene as a model to study neoplastic malignant growth. I have used genetic analysis to interrogate the Drosophila genome for genes that can be targeted to inhibit the development or arrest...

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Detalles Bibliográficos
Autor: Méndiz Manero, Mª Victoria
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/191601
Acceso en línea:https://hdl.handle.net/2445/191601
http://hdl.handle.net/10803/687262
Access Level:acceso abierto
Palabra clave:Oncologia
Tumors
Drosòfila melanogaster
Divisió cel·lular
Oncology
Drosophila melanogaster
Cell division
id ES_886c10dcb73bbc6fac98900dffd0dc7f
oai_identifier_str oai:diposit.ub.edu:2445/191601
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Identifying new targets to inhibit brat tumour growth in Drosophila melanogaster through combined transcriptomics and functional genome-wide analysis
title Identifying new targets to inhibit brat tumour growth in Drosophila melanogaster through combined transcriptomics and functional genome-wide analysis
spellingShingle Identifying new targets to inhibit brat tumour growth in Drosophila melanogaster through combined transcriptomics and functional genome-wide analysis
Méndiz Manero, Mª Victoria
Oncologia
Tumors
Drosòfila melanogaster
Divisió cel·lular
Oncology
Drosophila melanogaster
Cell division
title_short Identifying new targets to inhibit brat tumour growth in Drosophila melanogaster through combined transcriptomics and functional genome-wide analysis
title_full Identifying new targets to inhibit brat tumour growth in Drosophila melanogaster through combined transcriptomics and functional genome-wide analysis
title_fullStr Identifying new targets to inhibit brat tumour growth in Drosophila melanogaster through combined transcriptomics and functional genome-wide analysis
title_full_unstemmed Identifying new targets to inhibit brat tumour growth in Drosophila melanogaster through combined transcriptomics and functional genome-wide analysis
title_sort Identifying new targets to inhibit brat tumour growth in Drosophila melanogaster through combined transcriptomics and functional genome-wide analysis
dc.creator.none.fl_str_mv Méndiz Manero, Mª Victoria
author Méndiz Manero, Mª Victoria
author_facet Méndiz Manero, Mª Victoria
author_role author
dc.contributor.none.fl_str_mv González Hernández, Cayetano
Universitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació
dc.subject.none.fl_str_mv Oncologia
Tumors
Drosòfila melanogaster
Divisió cel·lular
Oncology
Drosophila melanogaster
Cell division
topic Oncologia
Tumors
Drosòfila melanogaster
Divisió cel·lular
Oncology
Drosophila melanogaster
Cell division
description [eng] I have used the brain tumours that originate in Drosophila larvae upon depletion of the brain tumor (brat) gene as a model to study neoplastic malignant growth. I have used genetic analysis to interrogate the Drosophila genome for genes that can be targeted to inhibit the development or arrest the growth of brat tumours. The targetable genome identified through this functional genomics approach includes 80 suppressors of brat tumour growth (brat-SPRs). I have also carried out transcriptomic analysis of brat tumours through which I have been able to define a brat tumour signature that includes 625 and 903 genes that are significantly up- and down-regulated in brat larval brain tumours compared to normal larval brains. From the combined analysis of my functional genomics and transcriptomics data I have concluded that correlation between the extent of gene expression dysregulation and function with regards to tumour development is so low that the former is not a good predictor of the latter. From the combined analysis of my own data on brat tumours and published functional genomics and transcriptomics data on the brain tumours that originate upon depletion of lethal(3)malignant brain tumor (l(3)mbt), henceforth referred to as mbt tumours, I have found that nearly 60% (47/80) of the brat-SPRs are tumour-type specific in the sense that they do not suppress mbt tumours. One of the non-tumour specific suppressors (i.e. mbt&brat-SPRs) identified in my study is Vacuolar protein sorting 26 (Vps26). Vps26 had been reported to be a type II neuroblast lineage-specific tumour suppressor. My results show that in addition, Vps26 function contributes to brat tumour growth and is essential for long-term survival of mbt tumours. My results also suggest that unlike its published tumour suppressor function, Vps26 mbt&brat-SPR activity might be independent of its role in the retromer complex.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/191601
http://hdl.handle.net/10803/687262
url https://hdl.handle.net/2445/191601
http://hdl.handle.net/10803/687262
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv (c) Méndiz Manero, Mª Victoria, 2022
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Méndiz Manero, Mª Victoria, 2022
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Facultat - Farmàcia i Ciències de l'Alimentació
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869412550539476992
spelling Identifying new targets to inhibit brat tumour growth in Drosophila melanogaster through combined transcriptomics and functional genome-wide analysisMéndiz Manero, Mª VictoriaOncologiaTumorsDrosòfila melanogasterDivisió cel·lularOncologyDrosophila melanogasterCell division[eng] I have used the brain tumours that originate in Drosophila larvae upon depletion of the brain tumor (brat) gene as a model to study neoplastic malignant growth. I have used genetic analysis to interrogate the Drosophila genome for genes that can be targeted to inhibit the development or arrest the growth of brat tumours. The targetable genome identified through this functional genomics approach includes 80 suppressors of brat tumour growth (brat-SPRs). I have also carried out transcriptomic analysis of brat tumours through which I have been able to define a brat tumour signature that includes 625 and 903 genes that are significantly up- and down-regulated in brat larval brain tumours compared to normal larval brains. From the combined analysis of my functional genomics and transcriptomics data I have concluded that correlation between the extent of gene expression dysregulation and function with regards to tumour development is so low that the former is not a good predictor of the latter. From the combined analysis of my own data on brat tumours and published functional genomics and transcriptomics data on the brain tumours that originate upon depletion of lethal(3)malignant brain tumor (l(3)mbt), henceforth referred to as mbt tumours, I have found that nearly 60% (47/80) of the brat-SPRs are tumour-type specific in the sense that they do not suppress mbt tumours. One of the non-tumour specific suppressors (i.e. mbt&brat-SPRs) identified in my study is Vacuolar protein sorting 26 (Vps26). Vps26 had been reported to be a type II neuroblast lineage-specific tumour suppressor. My results show that in addition, Vps26 function contributes to brat tumour growth and is essential for long-term survival of mbt tumours. My results also suggest that unlike its published tumour suppressor function, Vps26 mbt&brat-SPR activity might be independent of its role in the retromer complex.[spa] En este trabajo he utilizado los tumores cerebrales que se originan en larvas de Drosophila mutantes para el gen brain tumor (brat) como modelo para el estudio del crecimiento de neoplasias malignas. Mediante análisis genético he cribado el genoma de Drosophila en la búsqueda de genes cuya inactivación de lugar a la inhibición de la formación o del crecimiento sostenido de tumores brat. El conjunto de genes diana identificado a través de este enfoque de genómica funcional incluye 80 supresores de tumores brat (brat-SPRs). Así mismo he obtenido el transcriptoma de tumores brat de cuyo análisis he podido definir una “tumour signature” que incluye 625 and 903 genes cuya expresión está significativamente aumentada o disminuida en tumores brat con respecto a cerebros normales. Mediante el análisis combinado de mis resultados de genómica funcional y transcriptómica he podido concluir que la correlación entre el grado de desregulación de la expresión génica y la función del gen en relación con el desarrollo del tumor es tan reducida que el primer factor no puede ser utilizado para predecir el segundo. Del análisis combinado de mis datos sobre los tumores brat y de datos publicados de genómica funcional y transcriptómica de tumores cerebrales causados por la falta de función del gen lethal(3)malignant brain tumor (l(3)mbt) (“tumores mbt”) he observado que cerca del 60% (47/80) de los brat-SPRs son específicos de este tipo de tumor en el sentido de que su falta de función no suprime los tumores mbt. Uno de los supresores comunes para ambos tumores (mbt& brat-SPRs) identificados en mi trabajo es Vacuolar protein sorting 26 (Vps26). Datos publicados previamente demuestran que Vps26 funciona como supresor tumoral específicamente en el linaje de neuroblastos tipo II. Mis resultados revelan que, además, Vps26 contribuye al crecimiento de los tumores brat y es esencial para la supervivencia a largo plazo de los tumores mbt. Mis resultados también sugieren que a diferencia de su actividad como supresor tumoral, la función de Vps26 como mbt&brat-SPR parece ser independiente de su papel en el complejo del retrómero.Universitat de BarcelonaGonzález Hernández, CayetanoUniversitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació2022info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/191601http://hdl.handle.net/10803/687262Tesis Doctorals - Facultat - Farmàcia i Ciències de l'Alimentacióreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Méndiz Manero, Mª Victoria, 2022info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1916012026-05-27T06:46:51Z
score 15,300719

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