Dr Sonia Lopez de Quinto
Our work aims at elucidating the molecular mechanisms regulating mRNA translation in time and space. This post-transcriptional mode of gene regulation 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 embryonic body axis specification, 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.
Education and outreach
As an RCUK fellow, I significantly contribute to the outreach activities undertaken in the School of Biosciences. The general goal of my engagement is to showcase my research to school pupils to develop awareness of the benefits of using the fruit fly (Drosophila) as a model system to tackle essential biological and cellular functions with implications in human health.
I am also part of the STEM Ambassador Programme (which is run from the Techniquest Science Centre in Cardiff).
Some examples of my recent engagement with local schools:
Widening Access to Higher Education among under-represented groups
- Step-Up-to-Health event. "A Supermodel organism: Science from a FLY perspective". One-day workshop aimed at actively engaging with a group of 'A' level students about the nature, purpose and benefits of using Drosophila as a model organism in my research. See programme for further details.
- Demonstration on how we work with flies in the School, as part of a one-day workshop with around 40 'A' level students from Bridgend College.
- Summer Residential course, run by Hands On Science (an RCUK and Welsh Assembly funded widening access initiative), with pre-GCSE pupils. As part of a two-day event in the School, the visiting pupils participated in a workshop in the Drosophila group laboratory suite to highlight the collaborative work of the group and to examine genetically modified flies. See Innovation and Engagement Events for details of this workshop and the other research activities.
Annual "Learn About Life" event for visiting Primary schools
During National Science and Engineering Week: in this workshop the pupils visualise and draw their own stained cheek cells under the microscope.
Annual University Open Day
Drop-in demonstration for prospective students and their parents on the usage of fruit flies as a model organism for basic research.
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.
Regulation of mRNA translation in time and space
Many biological and cellular functions rely on the generation and maintenance of cell asymmetries, also known as cell polarity. Sub-cellular mRNA localization coupled to translation in a confined cytoplasmic region has emerged as a powerful mechanism to restrict protein synthesis in time and space, leading to the polarisation of the cell. Consistent with this, local translation of asymmetrically enriched mRNAs underlies essential biological functions such as embryonic development or synaptic plasticity. Furthermore, recent work has unravelled the role of RNA-based gene regulation in the development of human diseases such as cancer, genetic neurological disorders and viral infections. Thus, understanding the mechanisms governing formation and regulation of RNA-protein complexes (RNPs) is a pre-requisite for the design of new intervention strategies.
Using the fruit fly Drosophila as a genetically tractable model organism, and specifically the highly polarised oocyte, we have characterized different aspects of RNA regulation that control development of the future embryo's body axes. These regulatory mechanisms include the formation of transport-competent RNP particles, their interaction with the cytoskeleton, and the coordination between the transport and translation machineries.
Our recent work has revealed how the actin-based motor Myosin-V regulates the localization of oskar mRNA, the posterior determinant of the fly whose restricted expression at the posterior pole of the Drosophila oocyte is essential for the development of the future embryo. Our study has contributed to our understanding of how the actin and microtubule cytoskeletons cooperate for asymmetrical enrichment of an mRNA in a polarized cell (Krauss & Lopez de Quinto et al., 2009).
We have also identified and characterized two conserved RNA-binding proteins as key oskar regulators. Hrp48 binds to the 5´ and 3´ ends of oskar mRNA to regulate its transport to the posterior pole, while keeping the mRNA silent (Yano et al., 2004). In contrast, PTB binds preferentially to the oskar 3´UTR and, although dispensable for transport, it is essential for oskar mRNA translational repression. Our data points to PTB is a key structural component of oskar RNP complexes that functionally links formation of high-order RNP particles and translational silencing (Besse & Lopez de Quinto et al., 2009).
Our research interests
Hrp48 and PTB belong to the heterogeneous nuclear ribonucleoprotein family (hnRNP) of proteins. These general RNA-binding proteins associate with transcripts as they are synthesized and control multiple aspects of RNA processing, both in the nucleus and cytoplasm. Not surprisingly, changes in the activity of these general RNA-binding proteins are associated with a broad range of developmental and cellular defects, as well as human pathologies such as cancer. However, it is still not clear how hnRNP proteins discriminate among multiple RNA targets and most importantly, the mechanisms that these RNA-binding proteins employ to specifically regulate each RNA target.
Our work aims at elucidating the principles governing the assembly and dynamics of those RNP complexes that regulate the targeting and/or translation of asymmetrically enriched mRNAs. To this end, we are using functional assays to characterize in vivo the binding of several regulatory proteins to their specific RNA targets, in a genetically tractable model organism such as the fruit fly Drosophila melanogaster. This knowledge will allow us to predict and test how newly identified RNAs may be regulated by similar proteins. By identifying new targets of regulatory RNA-binding proteins we aim at discovering new cellular processes regulated by the local expression of RNAs. This will ultimately lead to the identification of potential targets for the design of therapeutic entities, enabling us to gain control of the expression of genes in the cell cytoplasm.
The general goals of our research include:
- Functional characterization of regulatory RNA-protein interactions.
- Identification of conserved RNA cis-acting motifs in asymmetrically localized mRNAs regulating their localization and translation.
- Identification of new regulatory trans-acting factors involved in the local translation of RNAs.
- Characterization of the cellular mechanisms underlying mRNA localization and translation regulation.
- Identification and characterization of new RNA targets associated with similar RNP complexes, using biochemical and computational approaches.
- Elucidation of the role that local expression of asymmetrically enriched RNAs plays in different cellular and developmental processes.
We are currently recruiting new lab members. Prospective post-doctoral fellows and PhD students should have suitable qualifications and CVs to compete for studentships/fellowships. If you are interested in our work do not hesitate to contact the lab firstname.lastname@example.org, sending your CV and a cover letter detailing your scientific interests.
Current grant support
RCUK Fellowship in Translational Research
Royal Society Research Grant