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Lab presentation

A new of centrosome-cilia in normal and pathological neural development

The centrosome is a membrane less organelle that gears fundamental roles in ensuring correct cell division, efficient primary cilia formation and normal neural tissue development. Defects in centrosome/cilia genes are directly linked to Neurodevelopment Disorders (NDDs) such as microcephaly, a rare, yet devastating condition caused by environmental insults or by genetic lesions.

The major research goal in our laboratory is to unravel some of the key mechanisms controlling proper neural development, from the centrosome/cilia axis to neurogenesis, in link with human brain evolution and disease. Our primary tools include the most in vivo dynamic system we can get our hands on; the embryonic chick neural tube as well as innovative models of organoids from human induced pluripotent stem cells, that recapitulate species-specific features of the central nervous system.

Projects

Centrosome/cilia axis as a central hub in Zika syndrome

Zika virus (ZIKV) infection, an Aedes mosquito-borne flavivirus, is declared a global threat for public health due to its association with congenital neurodevelopmental birth defects. Despite the enormous basic and clinical research efforts, no specific therapy has yet been approved for the treatment or prevention of ZIKV infection, thus a better understanding of the pathophysiology mechanisms is an urgent need.  Our recent studies of the effect of ZIKV non-structural (NS) -proteins on neural precursor cells (NPCs) proliferation, show that the ZIKV-NS5 protein interacts with host proteins at the base of the primary cilia, causing an atypical non-genetic ciliopathy and premature neuron delamination. One of our major aims is to provide high resolution vision of the ZIKV-NS5-cilia base proteins interactions, shedding new light into the mechanisms by which ZIKV-NS5 interferes with the molecular machinery of primary cilia formation and highlighting new potential targets for therapeutic intervention.

first project

Human-acquired centrosome-cilia genes, linking neurogenesis and evolution of central nervous system growth

Our aim is to elucidate the molecular and cellular mechanisms underlying the evolutionary expansion of the developing CNS and more precisely the increase in the number of NPCs generated during human embryonic CNS development. Novel insights on human CNS development and evolution may come from NDDs where species-specific developmental mechanisms have been affected. Recent discoveries have revealed a potential link of human-specific genes enriched in NPCs and the 1q21.1 syndrome, an NDD associated to abnormalities in head size and mental pathologies. This provides a unique opportunity to Interrogate the contribution of 1q21 human-specific genes in the evolutionary expansion of the human embryonic CNS, dissect the cellular mechanisms associated with the 1q21 human-specific genes and understand how de novo mutations or deletions of these genes impact neural development.

second project

Modelling neurodevelopmental disorders in human neural organoids

We study centrosome and cilia genes impact on human NPCs behavior displaying specific mutations causing NDDs. We combine technologies of induced pluripotent stem cells (iPSC), together with genomic editing or electroporation, in in vitro 3D organoid model of neurogenesis, developed in our and other labs (in collaboration with Dr. Reinald Shyti and Dr. Giuseppe Testa, from the Human Technopole, Milan, Italy). We aim to determine what are the cellular and molecular consequences of centrosome/cilia genes mutations in human neurogenesis, in order to define the pathophysiology mechanisms of NDDs, and how they may relate with species-specific mechanisms of human embryonic CNS development.

third project

Lab people

Principal Investigator

Murielle Saade is a Ramon y Cajal Research Investigator at IBMB. Her fascination to understand embryonic development started early in her scientific career and exponentially grow during her training in 4 different internationally recognized institutions from 4 different countries. After a BSc training at the University of Saint-Joseph-USJ (Lebanon), she moved to University of Aix-Marseille II (France), to carry out her Master and PhD studies under the supervision of Dr. Catherine Nguyen, to study embryonic thymus development and the generation of a correct and functional immune system. After her PhD, she joined the IBMB as a postdoctoral scientist, where she made seminal discoveries in elucidating the roles of the centrosome/ciliary axis in neurogenesis in health and disease.

In 2020, she started her career as a young PI, with the goal to elucidate the molecular and cellular mechanisms underlying the evolutionary human brain expansion. She seeks to understand human neurodevelopmental disorders  such as  microcephaly by studying the roles of centrosomes and primary cilia in cell division and tissue growth.

Past students

Selected publications

Murielle Saade, Diego S Ferrero, José Blanco-Ameijeiras, Elena Gonzalez-Gobartt, Victor M Ruiz-Arroyo, Elena Martínez-Sáez, Santiago Ramón y Cajal, Nuria Verdaguer and Elisa Martí (2020) Multimerization of Zika Virus-NS5 causes a ciliopathy and forces premature neurogenesis. Cell Stem Cell 27(6):920-936.e8. doi: 10.1016/j.stem.2020.10.002. https://pubmed.ncbi.nlm.nih.gov/33147489/

Highlighted in Nature Review Microbiol https://www.nature.com/articles/s41579-020-00481-9


Murielle Saade, Jose Blanco-Ameijeiras, Elena Gonzalez-Gobartt, and Elisa Martí (2018) A centrosomal view of CNS growth  Development 45(21):dev170613. doi: 10.1242/dev.170613  http://dev.biologists.org/content/145/21/dev170613


Murielle Saade, Elena Gonzalez-Gobartt, Rene Escalona, Susana Usieto and Elisa Martí (2017) Shh-mediated centrosomal recruitment of PKA promotes symmetric proliferative neuroepithelial cell division. Nature Cell Biology 19(5):493-503. doi:10.1038/ncb3512 http://www.nature.com/ncb/journal/v19/n5/abs/ncb3512.html


Murielle Saade, Irene Gutierrez, Gwenvael Le Dreau, M Angeles Rabadán, David G. Miguez, Javier Buceta and Elisa Martí (2013) Sonic hedgehog signaling switches the mode of division in the developing nervous system. Cell Reports 4(3):492-503. doi: 10.1016/j.celrep.2013.06.038.https://www.sciencedirect.com/science/article/pii/S2211124713003306?via%3Dihub

Highlighted in F1000  http://f1000.com/prime/718050366#recommendations-content

http://www.ncbi.nlm.nih.gov/pubmed/23891002

All publications

Murielle Saade, Diego S Ferrero, José Blanco-Ameijeiras, Elena Gonzalez-Gobartt, Victor M Ruiz-Arroyo, Elena Martínez-Sáez, Santiago Ramón y Cajal, Nuria Verdaguer and Elisa Martí (2020) Multimerization of Zika Virus-NS5 causes a ciliopathy and forces premature neurogenesis. Cell Stem Cell 27(6):920-936.e8. doi: 10.1016/j.stem.2020.10.002. https://pubmed.ncbi.nlm.nih.gov/33147489/

Highlighted in Nature Review Microbiol https://www.nature.com/articles/s41579-020-00481-9


Murielle Saade, Jose Blanco-Ameijeiras, Elena Gonzalez-Gobartt, and Elisa Martí (2018) A centrosomal view of CNS growth  Development 45(21):dev170613. doi: 10.1242/dev.170613  http://dev.biologists.org/content/145/21/dev170613


Murielle Saade, Elena Gonzalez-Gobartt, Rene Escalona, Susana Usieto and Elisa Martí (2017) Shh-mediated centrosomal recruitment of PKA promotes symmetric proliferative neuroepithelial cell division. Nature Cell Biology 19(5):493-503. doi:10.1038/ncb3512 http://www.nature.com/ncb/journal/v19/n5/abs/ncb3512.html


Herrera A, Saade M, Menendez A, Marti E, Pons S (2014) Sustained Wnt/β-catenin signalling causes neuroepithelial aberrations through the accumulation of aPKC at the apical pole. Nat Commun. 5:4168. doi: 10.1038/ncomms5168. https://www.nature.com/articles/ncomms5168


Le Dréau G, Saade M, Gutiérrez-Vallejo I, Martí E (2014) The strength of SMAD1/5 activity determines the mode of stem cell division in the developing spinal cord. J Cell Biol. 204(4):591-605. doi: 10.1083/jcb.201307031. https://rupress.org/jcb/article/204/4/591/37559/The-strength-of-SMAD1-5-activity-determines-the


Murielle Saade, Irene Gutierrez, Gwenvael Le Dreau, M Angeles Rabadán, David G. Miguez, Javier Buceta and Elisa Martí (2013) Sonic hedgehog signaling switches the mode of division in the developing nervous system. Cell Reports 4(3):492-503. doi: 10.1016/j.celrep.2013.06.038.https://www.sciencedirect.com/science/article/pii/S2211124713003306?via%3Dihub

Highlighted in F1000  http://f1000.com/prime/718050366#recommendations-content

http://www.ncbi.nlm.nih.gov/pubmed/23891002

Project funding

PROJECT TITLE: Understanding the Cellular Mechanisms of the 1q21.1 Neurodevelopmental Disorder

FINANCIAL ENTITY: GRT-2022A-2105

RESEARCH CENTER: Instituto de Biología Molecular de Barcelona (CSIC)

LENGTH: FROM DEL 09/2022 – 09/2024

AMOUNT GRANTED: 78.000€

PRINCIPAL INVESTIGATOR: Murielle Saade


PROJECT TITLE: UNDERSTAINDING THE MOLECULAR MECHANISMS UNDERLYING ZIKA VIRUS ASSOCIATED NEUROPATHY.

FINANCIAL ENTITY: PID2019-110157RA-I00.

RESEARCH CENTER: Instituto de Biología Molecular de Barcelona (CSIC)

LENGTH: FROM DEL 06/2020 – 06/2023

AMOUNT GRANTED: 118,000€

PRINCIPAL INVESTIGATOR: Murielle Saade

Proyecto PID2019-110157RA-I00 financiado por:


UNDERSTANDING THE MOLECULAR MECHANISMS UNDERLYING ZIKA VIRUS (ZIKV) INFECTION ASSOCIATION TO CONGENITAL MICROCEPHALY

FINANCIAL ENTITY: RYC2018-025379-I

RESEARCH CENTER: Instituto de Biología Molecular de Barcelona (CSIC)

AMOUNT GRANTED: 40,000€

PRINCIPAL INVESTIGATOR: Murielle Saade

Ayuda RYC2018-025379-I financiada por:

Vacancies/Jobs

The Saade team is welcoming application for a Postdoc position to unravel how the centrosome/cilia axis control neural precursor cells (NPCs) maintenance and differentiation during neurogenesis.

Research Background: Neurogenesis is a temporally and quantitatively highly balanced process which has to be tightly regulated, as even small alterations can have severe consequences for development and lead to neurodevelopmental disorders (NDDs). For example, microcephaly, one the most devastating type of brain size abnormality, starts with mutations and subsequent molecular dysregulations mostly at the two subcellular levels, the centrosome and the primary cilia which in consequence affect NPCs mode of division.

Research Objectives; Towards this goal, we take the following approaches:

  1. Dissect for genes related to the evolutionary composition of the centrosome-cilia axis in NPCs. We study the impact of these genes on the behavior of NPCs and their role in centrosome and cilia biology, in order to decipher their role as cell fate determinants for a correct evolutionary growth of the central nervous system (CNS).
  2. Dissect for pathogenic structural variants (pSVs) in association to particular NDDs such as microcephaly. We study the consequences of abnormal centrosome and ciliary function in human disease, with particular emphasis on the development of ciliopathies affecting the proper growth of CNS.

Research Environment: The host team has a long-range experience in the field of centrosome/cilia signaling in neural development, provide the unique scientific background and leadership capacities, to successfully address these questions of neural-specific centrosome proteins in human brain evolution and the acquisition of cognitive abilities. We are recognized for our expertise in studying neurodevelopment in vivo in the chick embryo neural tube and we are implementing human 3D tissue engineering in the lab. The postdoc will benefit from state-of-the-art tools and platforms available within the institute and on campus. The candidate will be supported by the team members at the scientific and technical level.

Your Profile: The candidate must have a good knowledge in tissue engineering, imaging, genetics and cellular biology. Basic Knowledge in bioinformatics will be helpful.

Please send your CV, a letter of motivation and contacts for references to: msabmc@ibmb.csic.es

Lab corner

  1. Introductions to the Community: Early-Career Researchers in the Time of COVID-19, Volume 28, Issue 2, 4 February 2021, Pages 184-186. https://www.sciencedirect.com/science/article/pii/S1934590921000126
  2. First online day for families with children 1q21. 1 deletion organized by the Sant Joan de Déu hospital. https://www.ibmb.csic.es/en/news/outreach/first-online-day-for-families-with-children-with-1q21-1-deletion-organized-by-the-sant-joan-de-deu-hospital/
  3. We share science, space, events and energy with the team of Dr. Elisa Marti!
Celebrating Sant Jordi April 23rd, 2021
Celebrating International Women's Day March 8th, 2022

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