Eva Maria Novoa (Centre for Genomic Regulation, CRG) has obtained an ERC Starting Grant 2021. Her project EpiSperm (Dissecting the role of sperm transcriptome dynamics in intergenerational inheritance through native RNA nanopore sequencing) will characterize the dynamics of RNA populations during sperm formation and maturation.
Eva Maria obtained her BSc in Biochemistry in 2007 and MSc in Bioinformatics in 2009 in Barcelona (Spain). Supported LaCaixa-IRB International PhD Program Fellowship, she then joined the Gene Translation Laboratory, led by Prof. Lluís Ribas de Pouplana at IRB Barcelona, to pursue a PhD in Biomedicine. Her research focused on the characterization of the translation machinery across species and its applications to drug discovery and led to propose that a critical factor that explains the differences between codon usage bias across species is the emergence of two domain-specific tRNA modification enzymes. In addition, during this stage she computationally designed and screened antimalarials that specifically target the malaria parasite’s translation machinery, finding positive hits that killed the parasite in vivo.
She relocated to the Computational Biology laboratory at Massachusetts Institute of Technology (USA) led by Prof. Manolis Kellis, where she developed novel machine learning algorithms to predict protein expression, deciphered rules for understanding codon usage bias as well as novel pipelines to study the RNA structurome. In 2017, she then relocated to the Garvan Institute of Medical Research (Australia) as a senior postdoctoral fellow. There, she received her first grant as an independent researcher to develop novel methods to map RNA modifications using nanopore sequencing.
Since 2018, she is Group Leader of the ‘Epitranscriptomics and RNA Dynamics’ laboratory at the Center for Genomic Regulation (CRG) in Spain. Her lab is focused on deciphering the language of RNA modifications, and how its orchestration can regulate our cells in a space-, time- and signal-dependent manner. Using a combination of experimental and computational techniques, her lab aims to unveil the secrets of three post-transcriptional regulatory layers: the epitranscriptome, RNA structure and ribosome specialization. Her laboratory has been a pioneer in the use of nanopore sequencing to study the epitranscriptome, including the development of novel algorithms to map and quantify RNA modifications, as well as novel library preparation protocols to study the dynamics of RNA populations in an unbiased and systematic manner.
Which are the main objectives of EpiSperm?
The main goal of EpiSperm is to dissect the molecular basis of RNA-mediated inheritance of environmental exposures, such as diet or stress, across generations. In this regard, recent works have shown that environmental inputs can reshape the sperm RNA signature and induce offspring phenotypes that relate to paternal environmental stressors. However, how, when and to what extent sperm RNA populations change, and what is the role that RNA modifications and other post-transcriptional regulatory layers play in shaping sperm RNA dynamics, remains poorly understood.
In EpiSperm, we propose to characterize the dynamics of RNA populations during sperm formation and maturation using native RNA nanopore sequencing. This technology is suited to provide an integrative and comprehensive view of the transcriptome, epitranscriptome, degradation patterns and tailing dynamics simultaneously, and with single-molecule resolution. We will establish novel nanopore-based library preparation methods that can capture the full sperm (epi)transcriptome, and will capitalize on our recently developed algorithms to map and quantify RNA modifications in individual RNA molecules. We will then apply these methods to reveal how paternal dietary exposures affect sperm RNA populations and the metabolic phenotypes of their offspring and test whether the novel identified RNA candidates can transmit diet-induced paternal phenotypes to the subsequent generation. Finally, we propose to expand our previous work on direct RNA multiplexing to establish single-cell direct RNA nanopore sequencing, to characterize the diversity and heterogeneity of the sperm RNA (epi)transcriptome at an unprecedented single-cell and single-molecule resolution.
Why did you decide to carry out your research at the Centre for Genomic Regulation?
The reasons for choosing CRG were very clear to me when I applied for a Group Leader position. Firstly, CRG is an internationally recognized research institute of scientific excellence. Secondly, its research topics greatly synergize with my own research, as reflected by several ongoing collaborations with several CRG labs. Thirdly, CRG offers excellent Core Facilities which have been key in pursuing my research projects.
How do you expect this grant will affect your professional career?
This will be a major boost in my career, both for the prestige that ERC grants have, as well as for the significant funding that comes with the grant, which makes it possible to conduct high risk-high gain research projects that otherwise would not be possible to conduct.
Are you planning to open research positions in your group?
Yes, I have already opened several research positions, including a position for a Lab Technician specialised in mice colony management, a postdoctoral position (ideally with a background in intergenerational inheritance and/or nanopore sequencing) and a PhD student position.
Are you planning any collaborations?
At the moment no. For the moment, I only have some internal collaborations with CRG Core Facilities planned (e.g. CRG Tissue Engineering Facility)
Where can we learn more about you and your project?
Website: https://www.crg.eu/ca/programmes-groups/novoa-lab
Twitter: @EvaMariaNovoa and @NovoaLab
Selected publications
Accurate detection of m6A RNA modifications in native RNA sequences, H. Liu, O. Begik, M.C. Lucas et al. Nat Commun 10, 4079, 2019.
Quaantitative profiling of pseudouridylation dynamics in native RNAs with nanopore sequencing, O. Begik, M.C. Lucas, L.P. Pryszcz et al. Nature Biotechnology 39, 1278-1291 (2021)
During the following weeks, we will be presenting those researchers working at Spanish institutions that have obtained an ERC Starting or Consolidator Grant 2021 and their projects. You can check their profiles HERE.
