GROUP DESCRIPTION

In our research we take advantage of C. elegans model system and other nematodes to provide new principles on neuron-type specification programs. We study its phylogenetic conservation combining the use of mouse models and study the mechanisms of evolution of neuronal novelties. We are also interested in gene regulatory networks controlling cell-fate homeostasis, resilience and plasticity. Some of the questions we want to address in the lab are: How are neuron-type genetic programs established at the molecular level? How is the neuronal regulatory genome decoded? How is the neuronal identity maintained throughout the life of the cell? How does environmental stimuli change neuron identity? Are these mechanisms phylogenetically conserved? What are the mechanisms that generate new neuronal types in evolution? Can we link specific defects in neuron type specification to genetic associations to disease?

GROUP OBJECTIVES

Our current research projects include:

1: Development of new tools for functional genomic studies in C. elegans at neuron type resolution.

2: Identification of conserved principles in gene regulatory networks driving neuron diversification.

3: Study of molecular mechanisms controlling neuron fate maintenance and plasticity to environmental stimuli.

4: Study the role of repressive mechanisms in promoting neuronal diversification.

5: Study post-transcriptional mechanisms driving neuronal differentiation.

6: Study of epigenetic factors controlling neuronal plasticity.

7: Molecular mechanisms underlying the evolution of neuronal diversity.

RESEARCH GROUP MEMBERS

Nuria Flame

Group leader

Rafael Alis

Postdoctoral researcher

Antonio Jordán

Postdoctoral researcher

Laura Chirivella

Lab manager

Maria Constanza Silvera

FPI Predoctoral researcher

Yaiza Dominguez Canterla

GVA ACIF Predoctoral researcher

Tam Nguyen

GVA Grisolia Predoctoral researcher

Sandra Pérez García

GVA ACIF Predoctoral researcher

Adrián Tarazona

GVA ACIF Predoctoral researcher

Irina María Hernández

Research technician

RESEARCH LINES

  1. Evolution of nervous system diversification.
  2. Gene regulatory networks controlling neuron fate establishment, maintenance and plasticity.

PROJECTS

  1. Dissecting the molecular mechanisms of serotonin reuptaker gene-expression plasticity. Plan Nacional PID2024-162563NB-I00. Length: 2025-2028. IP: Nuria Flames. Amount: 260.000 € + FPI
  2. Ayudas del programa Santiago Grisolía para la promoción de la investigación científica, el desarrollo tecnológico y la innovación en la comunitat Valenciana. Generalitat Valenciana CIGRIS/2023/193. Length: 2025-2028. IP: Nuria Flames. Amount: 99.675,00 €. Contrato de personal.
  3. Transcriptional regulatory programs controlling neuron morphology and neuronal resilience. Generalitat Valenciana CIAICO/2022/195. Length: 2023-2025. IP: Nuria Flames. Amount: 90.000 €
  4. Regulatory rules and evolution of neuronal gene expression. ERC Consolidator Grant NEUROCODE 101002203. Agency: European Research Council. Participating Entities: Instituto Biomedicina de Valencia. Length: 2021-2026. IP: Nuria Flames;. Amount: 1.997.500 Euros
  5. Especificación, evolución y plasticidad de tipos neuronales con importancia biomédica. PID2020-115635RB-I00. Agency: Ministerio de Ciencie e Innovación.  Length: 2021-2024. IP: Flames, Nuria; Amount: 217.800 Euros
  6. Papel de la traducción génica en la activación de las células madre adultas. PROMETEO/2018/055. Agency: Generalitat Valenciana. Participating Entities: Instituto Biomedicina de Valencia. Length: 2018-2021. IPs: Pérez-Tur, Jordi ;Vilar, Marçal ;Bravo, Jeronimo ;Casado, Marta ;Flames, Nuria ;. Amount: 315.500 Euros. IP coordinador: Mira, Helena
  7. Subvenciones para mejorar la formación y empleabilidad de personal técnico y de gestion I+D+I (Garantía Juvenil). Generalitat Valenciana, GJIDI/2018/A/187. IP: Flames, Nuria. Amount: 48.5984 €. Contrato de personal
  8. Programas de regulación transcripcional asociados a enfermedades genéticas. Agency: MINECO, SAF2017-84790-R. Participating Entities: Instituto Biomedicina de Valencia. Length: 2018-2020. IP: Nuria Flames. 242.000 Euros + FPI
  9. Estudio de los mecanismos transcripcionales que regulan la diferenciación de las neuronas monoaminérgicas y su conservación evolutiva. Agency: MINECO, SAF2014-56877-R. Participating Entities: Instituto Biomedicina de Valencia. Length: 2015-2017. IP: Nuria Flames. Amount: 242.000 Euros + FPI
  10. Dissecting the gene regulatory mechanisms that generate serotonergic neurons and their link to mental disorders. Agency: European Research Council. Starting Grant. Participating Entities: Instituto Biomedicina de Valencia. Length: 2012-2018. IP: Nuria Flames. Amount: 1.931.621 €
  11. Ayudas para la contratación de personal de Apoyo en centros de investigación de la comunitat valenciana. Programa Gerónimo Forteza. Generalitat Valenciana, FPA/2014/099. Length: 2012-2014. IP: Nuria Flames. Amount: 8.100€, contrato de personal
  12. Unraveling the molecular mechanisms that generate serotonergic neurons. Agency: Ministerio de Ciencia e Innovación. Proyectos de Investigación Fundamental no orientada, SAF2011-26273. Participating Entities: Instituto Biomedicina de Valencia. Length: 2014. IP: Nuria Flames.
  13. Dissecting the gene regulatory mechanisms that generate serotonergic neurons. Agency: Research Executive Agency. Marie Curie Actions. Career Integration Grants. Participating Entities: Instituto Biomedicina de Valencia. Length: 2011-2015. IP: Nuria Flames. Amount: 100.000 Euros
  14. Gene regulatory mechanisms that generate serotonergic neurons. Agency: National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD). Participating Entities: Columbia University and Instituto Biomedicina de Valencia. Length: 2011-2013. IP: Nuria Flames. Amount: 60.000 US $
  15.  Direct reprogramming of cells into dopaminergic neurons. Agency: Michael J. Fox Foundation. Rapid Response Innovation Award. Participating Entities: Columbia University. Length: 2011-2012. IP: Nuria Flames. Amount: 75.000 US$.

PUBLICATIONS

  1. Andrea Millán-Trejo#, Carlos Mora-Martínez#, Adrián Tarazona-Sánchez, Carla Lloret-Fernández, Rafael Alis, Antonio Jordán, Arantza Barrios and Nuria Flames*.. Epigenetic constraint and enhancer innovation link neuronal plasticity to evolutionary adaptation. PNAS, in press. https://doi.org/10.1101/2025.01.30.635650. #: co-first
  2. Koyuncu S, Dominguez-Canterla Y, Alis R, Salarzai N, Petrovic D, Flames N, Vilchez D. The aging factor EPS8 induces disease-related protein aggregation through RAC signaling hyperactivation. Nat Aging. 2025 Sep;5(9):1750-1770. doi: 10.1038/s43587-025-00943-w.
  3. Moissidis M, Abbasova L, Selten M, Alis R, Bernard C, Domínguez-Canterla Y, Oozeer F, Qin S, Kelly A, Mòdol L, Vasistha NA, Jones B, Dhami P, Khodosevich K, Hamid F, Lavender P, Flames N, Marín O. A postnatal molecular switch drives activity-dependent maturation of parvalbumin interneurons. Cell. 2025 Oct 2;188(20):5555-5575.e26. doi: 10.1016/j.cell.2025.06.029.
  4. Poole RJ*, Flames N*, Cochella L*. Neurogenesis in Caenorhabditis elegans. Genetics. 2024 Aug 21:iyae116. doi: 10.1093/genetics/iyae116. .* Co-corresponding authors. Wormbook Chapter Invited.
  5. Brocal-Ruiz R, Esteve-Serrano A, Mora-Martínez C, Franco-Rivadeneira ML, Swoboda P, Tena JJ, Vilar M, Flames N*. Forkhead transcription factor FKH-8 cooperates with RFX in the direct regulation of sensory cilia in Caenorhabditis elegans. 2023 Jul 14;12:e89702. doi: 10.7554/eLife.89702. Traditional eLife ACCEPTED/REJECTED track.
  6. Jimeno-Martín A, Sousa E, Daroqui N, Brocal-Ruiz R, Maicas M, Flames N*. Transcription factors from multiple families ensure enhancer selectivity and robust neuron terminal differentiation. Genome Res. 2022 Mar;32(3):459-473. doi: 10.1101/gr.275623.121.
  7. Miren M., Jimeno-Martín A., Millán-Trejo A., Alkema and Flames N*. Notch independent functions of LAG-1/CSL control terminal differentiation, maintenance and gene expression plasticity of a chemosensory neuron. PLOS Biology, 2021 Jul 7;19(7):e3001334.
  8. Remesal L., Roger-Banyat I., Chirivella L., Maicas M., Brocal-Ruiz R., Pérez-Villalva A., Cucarella C., Casado M., Flames N*. PBX1 is a terminal selector of olfactory bulb dopaminergic neurons. Development, 2020 Apr 13;147(8):dev186841. doi: 10.1242/dev.186841.,
  9. Aydin B., Kakumanu A., Rossillo M., Moreno-Estellés M., Garipler G., Ringstad N., Flames N., Mahony S. and Mazzoni E.O. Proneural factors Ascl1 and Neurog2 contribute to neuronal subtype identities by establishing distinct chromatin landscapes. Nature Neuroscience. 2019 Jun;22(6):897-908.
  10. Lloret-Fernandez C, Maicas M, Mora-Martinez C, Artacho A, Jimeno-Martín Á, Weinberg P, Flames N*. A transcription factor collective defines the HSN serotonergic neuron regulatory landscape. eLife. 2018. Traditional eLife ACCEPTED/REJECTED track.