Dr Sonia Lopez De Quinto
Uwch Ddarlithydd
Ysgol y Biowyddorau
- Ar gael fel goruchwyliwr ôl-raddedig
Trosolwyg
My group studies the molecular mechanisms regulating mRNA translation in time and space. Our focus is on understanding the role of conserved RNA-binding proteins in these processes, as well as the molecular code governing RNA-protein complex formation and how these complexes define where specific mRNA transcripts engage with cytoplasmic ribosomes for protein synthesis.
This type of post-transcriptional gene expression regulation in the cell cytoplasm allows cells to respond quickly to external stimuli and plays a pivotal role in the establishment and maintenance of cell polarity. mRNA targeting coupled to translational control underlies essential biological processes such as body axis formation during development, morphogen secretion, synaptic plasticity, cell migration and thus, tumour invasiveness.
Using Drosophila as a model system and a variety of techniques, we seek to identify and functionally characterize in vivo localized mRNAs sharing similar regulatory networks.
Roles
- Senior Personal Tutor
- Admissions Tutor (Biochemistry)
- Assessment Leader BI3254 Genes to Genomes
Interested in joining my lab as a self-funded post-graduate student or a postdoc/fellow? Please contact me by email.
Cyhoeddiad
2009
- Krauss, J., Lopez De Quinto, S., Nusslein-Volhard, C. and Ephrussi, A. 2009. Myosin-V regulates oskar mRNA localization in the drosophila oocyte. Current Biology 19(12), pp. 1058-1063. (10.1016/j.cub.2009.04.062)
- Besse, F., Lopez de Quinto, S., Marchand, V., Trucco, A. and Ephrussi, A. 2009. Drosophila PTB promotes formation of high-order RNP particles and represses oskar translation. Genes & Development 23(2), pp. 195-207. (10.1101/gad.505709)
- Pacheco, A., Lopez De Quinto, S., Ramajo, J., Fernandez, N. and Martinez-Salas, E. 2009. A novel role for Gemin5 in mRNA translation. Nucleic Acids Research 37(2), pp. 582-590. (10.1093/nar/gkn979)
- Fernandez-Miragall, O., Lopez de Quinto, S. and Martinez-Salas, E. 2009. Relevance of RNA structure for the activity of picornavirus IRES elements. Virus Research 139(2), pp. 172-182. (10.1016/j.virusres.2008.07.009)
2005
- Lopez De Quinto, S., Martínez-Salas, E., Pacheco, A. and Reigadas, S. 2005. Specific interference between two unrelated internal ribosome entry site elements impairs translation efficiency. FEBS Letters 579(30), pp. 6803-6808. (10.1016/j.febslet.2005.11.015)
2004
- Lopez De Quinto, S., Ephrussi, A., Shevchenko, A. and Yano, T. 2004. Hrp48, a Drosophila hnRNPA/B Homolog, Binds and Regulates Translation of oskar mRNA. Developmental Cell 6(5), pp. 637-648. (10.1016/S1534-5807(04)00132-7)
2002
- Lopez De Quinto, S., Sáiz, M., De La Moreno, D., Sobrino, F. and Martinez-Salas, E. 2002. IRES-driven translation is stimulated separately by the FMDV 3'-NCR and poly(A) sequences.. Nucleic Acids Research 30(20), pp. 4398-4405. (10.1093/nar/gkf569)
- Martinez-Salas, E., Lopez De Quinto, S., Ramos, R. and Fernandez-Miragall, O. 2002. IRES elements: features of the RNA structure contributing to their activity. Biochimie 84(8), pp. 755-763. (10.1016/S0300-9084(02)01408-6)
2001
- Lopez De Quinto, S., Lafuente, E. and Martínez-Salas, E. 2001. IRES interaction with translation initiation factors: Functional characterisation of novel RNA contacts with eIF3, elF4B and eIF4GII. RNA 7(9), pp. 1213-1226. (10.1017/S1355838201010433)
- Martinez-Salas, E., Ramos, R., Lafuente, E. and Lopez De Quinto, S. 2001. Functional interactions in internal translation initiation directed by viral and cellular IRES elements. Journal of General Virology 82(5), pp. 973-984.
2000
- Lopez De Quinto, S. and Martinez-Salas, E. 2000. Interaction of the eIF4G initiation factor with the aphthovirus IRES is essential for internal translation initiation in vivo. RNA 6(10), pp. 1380-1392. (10.1017/S1355838200000753)
1999
- Lopez De Quinto, S. and Martinez-Salas, E. 1999. Involvement of the aphthovirus RNA region located between the two functional AUGs in start codon selection. Virology 255(2), pp. 324-336. (10.1006/viro.1999.9598)
- Saiz, J. C., Lopez De Quinto, S., Ibarrola, N., Lopez-Labrador, F. X., Sanchez-Tapias, J. -., Rodes, J. and Martinez-Salas, E. 1999. Internal initiation of translation efficiency in different hepatitis C genotypes isolated from interferon treated patients. Archives of Virology 144(2), pp. 215-229. (10.1007/s007050050499)
1998
- Lopez De Quinto, S. and Martinez-Salas, E. 1998. Parameters in influencing translational efficiency in aphthovirus IRES-based bicistronic expression vectors. Gene 217(1-2), pp. 51-56. (10.1016/S0378-1119(98)00379-5)
Articles
- Krauss, J., Lopez De Quinto, S., Nusslein-Volhard, C. and Ephrussi, A. 2009. Myosin-V regulates oskar mRNA localization in the drosophila oocyte. Current Biology 19(12), pp. 1058-1063. (10.1016/j.cub.2009.04.062)
- Besse, F., Lopez de Quinto, S., Marchand, V., Trucco, A. and Ephrussi, A. 2009. Drosophila PTB promotes formation of high-order RNP particles and represses oskar translation. Genes & Development 23(2), pp. 195-207. (10.1101/gad.505709)
- Pacheco, A., Lopez De Quinto, S., Ramajo, J., Fernandez, N. and Martinez-Salas, E. 2009. A novel role for Gemin5 in mRNA translation. Nucleic Acids Research 37(2), pp. 582-590. (10.1093/nar/gkn979)
- Fernandez-Miragall, O., Lopez de Quinto, S. and Martinez-Salas, E. 2009. Relevance of RNA structure for the activity of picornavirus IRES elements. Virus Research 139(2), pp. 172-182. (10.1016/j.virusres.2008.07.009)
- Lopez De Quinto, S., Martínez-Salas, E., Pacheco, A. and Reigadas, S. 2005. Specific interference between two unrelated internal ribosome entry site elements impairs translation efficiency. FEBS Letters 579(30), pp. 6803-6808. (10.1016/j.febslet.2005.11.015)
- Lopez De Quinto, S., Ephrussi, A., Shevchenko, A. and Yano, T. 2004. Hrp48, a Drosophila hnRNPA/B Homolog, Binds and Regulates Translation of oskar mRNA. Developmental Cell 6(5), pp. 637-648. (10.1016/S1534-5807(04)00132-7)
- Lopez De Quinto, S., Sáiz, M., De La Moreno, D., Sobrino, F. and Martinez-Salas, E. 2002. IRES-driven translation is stimulated separately by the FMDV 3'-NCR and poly(A) sequences.. Nucleic Acids Research 30(20), pp. 4398-4405. (10.1093/nar/gkf569)
- Martinez-Salas, E., Lopez De Quinto, S., Ramos, R. and Fernandez-Miragall, O. 2002. IRES elements: features of the RNA structure contributing to their activity. Biochimie 84(8), pp. 755-763. (10.1016/S0300-9084(02)01408-6)
- Lopez De Quinto, S., Lafuente, E. and Martínez-Salas, E. 2001. IRES interaction with translation initiation factors: Functional characterisation of novel RNA contacts with eIF3, elF4B and eIF4GII. RNA 7(9), pp. 1213-1226. (10.1017/S1355838201010433)
- Martinez-Salas, E., Ramos, R., Lafuente, E. and Lopez De Quinto, S. 2001. Functional interactions in internal translation initiation directed by viral and cellular IRES elements. Journal of General Virology 82(5), pp. 973-984.
- Lopez De Quinto, S. and Martinez-Salas, E. 2000. Interaction of the eIF4G initiation factor with the aphthovirus IRES is essential for internal translation initiation in vivo. RNA 6(10), pp. 1380-1392. (10.1017/S1355838200000753)
- Lopez De Quinto, S. and Martinez-Salas, E. 1999. Involvement of the aphthovirus RNA region located between the two functional AUGs in start codon selection. Virology 255(2), pp. 324-336. (10.1006/viro.1999.9598)
- Saiz, J. C., Lopez De Quinto, S., Ibarrola, N., Lopez-Labrador, F. X., Sanchez-Tapias, J. -., Rodes, J. and Martinez-Salas, E. 1999. Internal initiation of translation efficiency in different hepatitis C genotypes isolated from interferon treated patients. Archives of Virology 144(2), pp. 215-229. (10.1007/s007050050499)
- Lopez De Quinto, S. and Martinez-Salas, E. 1998. Parameters in influencing translational efficiency in aphthovirus IRES-based bicistronic expression vectors. Gene 217(1-2), pp. 51-56. (10.1016/S0378-1119(98)00379-5)
Ymchwil
Rheoleiddio cyfieithu mRNA mewn amser a gofod
Mae llawer o swyddogaethau biolegol a cellog yn dibynnu ar gynhyrchu a chynnal anghymesureddau celloedd, a elwir hefyd yn polaredd celloedd. Mae lleoleiddio mRNA is-gellog ynghyd â chyfieithu mewn rhanbarth cytoplasmig cyfyng wedi dod i'r amlwg fel mecanwaith pwerus i gyfyngu synthesis protein mewn amser a gofod, gan arwain at bolareiddio'r gell. Yn gyson â hyn, mae cyfieithu lleol o mRNAs a gyfoethogwyd yn anghymesur yn sail i swyddogaethau biolegol hanfodol fel datblygiad embryonig neu blastigrwydd synaptig. Ar ben hynny, mae gwaith diweddar wedi dadrithio rôl rheoleiddio genynnau yn seiliedig ar RNA yn natblygiad clefydau dynol fel canser, anhwylderau niwrolegol genetig a heintiau firaol. Felly, mae deall y mecanweithiau sy'n llywodraethu ffurfio a rheoleiddio cyfadeiladau RNA-protein (RNPs) yn rhagofyniad ar gyfer dylunio strategaethau ymyrraeth newydd.
Gwaith blaenorol
Gan ddefnyddio'r pryfyn ffrwythau Drosophila fel organeb model sy'n gludadwy yn enetig, ac yn benodol yr oocyte polar iawn, rydym wedi nodweddu gwahanol agweddau ar reoleiddio RNA sy'n rheoli datblygiad bwyeill corff embryo y dyfodol. Mae'r mecanweithiau rheoleiddio hyn yn cynnwys ffurfio gronynnau RNP sy'n gymwys o ran cludiant, eu rhyngweithio â'r cytosgerbwd, a'r cydgysylltiad rhwng y peiriannau cludo a chyfieithu.
Mae ein gwaith wedi cyfrannu at ein dealltwriaeth o sut mae'r actin a'r cytosgerbydau microtubule yn cydweithio i gyfoethogi anghymesur mRNAs yn ooocyte Drosophila (Krauss & Lopez de Quinto et al., 2009).
Rydym hefyd wedi nodi a nodweddu dau brotein RNA rhwymo a gadwyd fel rheoleiddwyr oskar allweddol. Mae Hrp48 yn rhwymo i ben 5 'a 3' oskar mRNA i reoleiddio ei gludiant i'r polyn ôl, tra'n cadw'r mRNA yn dawel (Yano et al., 2004). Mewn cyferbyniad, mae PTB yn rhwymo'n ffafriol i'r oskar 3'UTR ac, er ei fod yn anhepgor ar gyfer trafnidiaeth, mae'n hanfodol ar gyfer gormes drosiadol oskar mRNA. Mae ein pwyntiau data i PTB yn elfen strwythurol allweddol o oskar Cyfadeiladau RNP sy'n cysylltu'n swyddogaethol â ffurfio gronynnau RNP trefn uchel a silencing trosiadol (Besse & Lopez de Quinto et al., 2009).
Ein diddordebau ymchwil
Mae Hrp48 a PTB yn perthyn i'r teulu ribonucleoprotein niwclear heterogenaidd (hnRNP) o broteinau. Mae'r proteinau RNA rhwymo cyffredinol hyn yn cysylltu â thrawsgrifiadau gan eu bod yn cael eu syntheseiddio ac yn rheoli sawl agwedd ar brosesu RNA, yn y cnewyllyn a'r cytoplasm. Nid yw'n syndod bod newidiadau yng ngweithgaredd y proteinau RNA rhwymo cyffredinol hyn yn gysylltiedig ag ystod eang o ddiffygion datblygiadol a chellol, yn ogystal â batholegau dynol fel canser. Fodd bynnag, nid yw'n glir o hyd sut mae proteinau hnRNP yn gwahaniaethu ymhlith sawl targed RNA ac yn bwysicaf oll, y mecanweithiau y mae'r proteinau RNA rhwymo hyn yn eu defnyddio i reoleiddio pob targed RNA yn benodol.
Nod ein gwaith yw egluro'r egwyddorion sy'n llywodraethu cynulliad a deinameg y cymhlethdodau RNP hynny sy'n rheoleiddio targedu a / neu gyfieithu mRNAs cyfoethog anghymesur. I'r perwyl hwn, rydym yn defnyddio profion swyddogaethol i nodweddu yn vivo rhwymo sawl protein rheoleiddio i'w targedau RNA penodol, mewn organeb model sy'n gludadwy yn enetig fel y pryf ffrwythau Drosophila melanogaster. Bydd y wybodaeth hon yn ein galluogi i ragweld a phrofi sut y gellir rheoleiddio RNAs sydd newydd eu hadnabod gan broteinau tebyg. Trwy nodi targedau newydd o broteinau RNA sy'n rhwymo rheoliadau rydym yn anelu at ddarganfod prosesau cellog newydd a reoleiddir gan fynegiant lleol RNAs. Yn y pen draw, bydd hyn yn arwain at nodi targedau posibl ar gyfer dylunio endidau therapiwtig, Ein galluogi i ennill rheolaeth ar fynegiant genynnau yn y cytoplasm celloedd.
Amcanion ein hymchwil yw:
- Nodweddu swyddogaethol rhyngweithio RNA-protein rheoleiddiol.
- Adnabod motiffau gweithredu cis-RNA wedi'u cadw mewn mRNAs lleol anghymesur rheoleiddio eu lleoleiddio a'u cyfieithu.
- Adnabod ffactorau traws-weithredu rheoleiddiol newydd sy'n ymwneud â chyfieithu RNAs yn lleol.
- Nodweddu'r mecanweithiau cellog sy'n sail i leoleiddio mRNA a rheoleiddio cyfieithu.
- Adnabod a nodweddu targedau RNA newydd sy'n gysylltiedig â chyfadeiladau RNP tebyg, gan ddefnyddio dulliau biocemegol a chyfrifiannol.
- Eglurhad o'r rôl y mae mynegiant lleol o RNAs a gyfoethogwyd yn anghymesur yn ei chwarae mewn gwahanol brosesau cellog a datblygiadol.
Aelodau presennol y Lab
- Abdulla Almoalem (2019-presennol), myfyriwr PhD a ariennir gan lywodraeth Emiradau Arabaidd Unedig.
- Nehad Silan (2022-presennol), myfyriwr PhD a ariennir gan lywodraeth Saudi Arabia.
- Caleb Huntley-Welsenaer (2023-2024), myfyriwr Meistr Integredig.
Mentoriaid ymchwil a chydweithwyr
- Encarnación Martínez-Salas (CBMSO, Cyngor Ymchwil Cenedlaethol Sbaen, Sbaen)
- Anne Ephrussi (EMBL Heidelberg, yr Almaen)
- Carolina Pérez-Iratxeta - Sefydliad Ymchwil Iechyd Ottawa, Ottawa (Canada)
- Will Wood (Prifysgol Caeredin)
Addysgu
- BI2232 - Biochemistry
- BI2234 - Molecular Biology of the Gene
- Year 2 - Week Long Practical - From Foods to Pharmaceuticals: The Promise of Recombinant Alginate Lyases
- BI3254 - Genes to Genomes
Bywgraffiad
Career profile
I graduated in 1995 with a BA in Science (Chemistry) from Universidad Autónoma de Madrid (Spain), where I also carried out my PhD. In 2002 I joined the EMBL Heidelberg (Germany) for my post-doctoral studies and moved to the School of Biosciences at Cardiff University in December 2007, with support by a RCUK Fellowship in Translational Research in Experimental Medicine.
My long-standing research interests focus on gene expression regulation, with a special emphasis on those mechanisms operating at the mRNA level. Recent findings have highlighted the crucial role that RNA regulation has in tuning the expression of batteries of genes that the cell requires for specific tasks. However, our knowledge of the molecular mechanisms operating at different levels to regulate the expression and fate of mRNAs remains limited.
During my Masters and PhD research (Madrid, Spain), I analysed the mechanism employed by a highly specialized viral RNA region called IRES (Internal Ribosome Entry Site) to recruit the translational machinery to an internal start codon. My work led to the identification of conserved RNA motifs involved in the three-dimensional folding of the IRES and in the establishment of RNA-protein interactions that are essential for translation initiation. This work significantly contributed to the understanding of how gene expression regulation is achieved in RNA viruses.
During my postdoctoral studies at the EMBL (Heidelberg, Germany), I developed a deep interest in the impact that RNA regulation has on the cellular processes ultimately regulating development and disease progression. Specifically, I studied the mechanisms underlying the asymmetric distribution in the oocyte of cell fate determinants, which define the body axes of the future embryo. Over the last years, I characterized in vivo the role of key regulators of oskar mRNA post-transcriptional regulation, such as the cytoskeletal components cooperating in the asymmetrical enrichment of an mRNA in a polarized cell, and the RNA-binding proteins and cis-acting RNA motifs coordinating the transport of an mRNA to its translational control. These results have been crucial to understand the mechanisms operating on asymmetrically enriched mRNAs to control their sub-cellular targeting and local expression.
Professional memberships
Fellow of the Higher Education Academy
Member of the British Society for Developmental Biology
Member of the Biochemical Society
Member of the Spanish Society of Biochemistry and Molecular Biology
Aelodaethau proffesiynol
Fellow of the Higher Education Academy
Member of the British Society for Developmental Biology
Member of the Biochemical Society
Member of the Spanish Society of Biochemistry and Molecular Biology
Meysydd goruchwyliaeth
Research in my lab revolves around the themes listed below. If this is of interest to you, please contact me so we can generate a project outline together.
- RNA Biology
- RNA binding proteins (RBP)
- RNA localisation
- Translation regulation
- Developmental Cell Biology
- Post-transcriptional regulation of gene expression
Current PhD projects as Main Supervisor:
- Abdulla Almoalem (2019-current), funded by United Arab Emirates government.
- Nehad Silan (2022-current), funded by Saudi Arabian government.
Current PhD projects as Second Supervisor:
- Dana Jackson (2020-current), BBSRC SWBio PhD DTP studentship.
Goruchwyliaeth gyfredol
Abdulla Omar Almoalem Almoalem
Myfyriwr ymchwil
Nehad Saleh S. Silan
Myfyriwr ymchwil
Ymgysylltu
ArrayContact Details
+44 29208 79008
Adeilad Syr Martin Evans, Ystafell W/3.20, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX