Molecular mechanisms balancing the output of ciliary TGFβ/BMP signaling


 

Jindriska Leischner Fialová (ESR5)

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Jindriska comes from Czech Republic, where she obtained her undergraduate degree in Applied Biochemistry at Masaryk University. She continued with her studies at the same university and got her master’s degree in Analytical Biochemistry. While studying, she worked in laboratory of Dr. Michal Masařík, where she assessed biological effects of newly synthesized anti-cancer agents, especially their anti-migratory activity. In 2019, she spent six months as an intern at the Centre de Recherche en cancérologie de Marseille, France. There she worked on the characterisation of perinuclear actin-septin network and its role in cell migration. After this experience she decided to continue in her studies abroad and decided to pursue her PhD in the Cilia Group, University of Copenhagen under supervision of Dr. Søren Tvorup Christensen.

In February 2024, she has successfully defended her PhD thesis “Molecular mechanisms balancing the output of ciliary TGFB/BMP signaling” and obtained her PhD in March 2024 from University of Copenhagen. During summer 2024 she had been awarded with postdoctoral fellowship at Institute of Science and Technology Austria (ISTA), where she is currently working on “Deciphering the cellular basis of BMP gradient formation in the developing neural tube”.

What does Jindriska say about our program?

I am extremely grateful for the opportunity to be part of our SCilS consortium. This program meant so much for me as it allowed me to grow as a scientist and also as a person. The fact that at the beginning you are at the beginning of your journey with 13 other people going through exactly the same struggles as you are, makes making friendships very easy and natural. And I believe that long lasting friendships were made. Another important aspect of our program were our exchanges and meetings which always opened up our eyes and showed us a new perspective on our own research and cilia field. Thanks to our SCilS program I have tons of amazing memories and connections which I could not got otherwise.

Abstract
TGFβ/BMP signaling controls a complex network of spatiotemporal signaling pathways, which when dysregulated are major causes of developmental disorders and cancer. This signaling is coordinated by primary cilia and that activation of downstream signaling pathways is coupled to intraciliary trafficking as well as internalization and recycling of receptors at the ciliary base. However, the mechanisms underlying these trafficking events are largely unknown. ESR5 will decipher the molecular mechanisms by which primary cilia balance the output of diverse TGFβ/BMP pathways to control cellular and developmental processes using high resolution fluorescence microscopy and live cell imaging of cultures of wild type and CRISPR/Cas9-generated knockout cells. She will study the role of protein RRP7A, which has been shown to locate at the ciliary base and cells with mutated RRP7A display hyperactivated TGFβ signaling whereas BMP signaling is repressed. Proteomics/data analyses will be done in collaboration with P7-EKUT/P10-CellNetworks, respectively. In collaboration with ESR12, she will translate how ciliary trafficking events control developmental processes guided by TGFβ/BMP signaling in zebrafish.


We want you to understand!

Layman abstract

Decoding the mysteries of a developing brain

Patients with a mutation in RRP7A have reduced brain size and intellectual disability. RRP7A is a protein with an important role in protein synthesis, but it can be also found in primary cilium, antenna of the cell, where we do not know its function. In my project, I try to figure out what goes wrong inside cells with this mutation and what function RRP7A has at the ciliary level. This will help to better understand how brain develops and potentially could improve prenatal genetic screening for neurodevelopmental diseases.

You can also watch a 55-sec video which Jindriska created to describe her research here: YOUTUBE or with others on our website here.