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Blanco-Redondo Lab

​​​​​The ability to precisely modify genetic sequences in Drosophila melanogaster has revolutionized the study of molecular structure-function relationships in this powerful model organism. The use of CRISPR/Cas9, combined with recombinase systems like the bacteriophage serine integrase ΦC31, has streamlined Drosophila mutagenesis—enabling targeted deletions, insertions, and modifications to uncover the functional significance of genetic elements. Our research focuses on unraveling the role of Remoulade (Remo), a recently discovered adhesion GPCR (aGPCR) in Drosophila, with potential implications for future drug development. Additionally, we explore the genetic underpinnings of rare neurodegenerative diseases such as NEDCAM (Neurodevelopmental Disorder with Cerebellar Atrophy and Motor Dysfunction). Leveraging Drosophila's powerful genetic toolkit, we generate knock-outs, knock-ins, and transgenic lines to investigate gene function, expression patterns, and phenotypic consequences—paving the way for groundbreaking discoveries in neuroscience and beyond.​​

Contact

Dr. Beatriz Blanco-Redondo

E-Mail: Beatriz.Blanco-Redondo@medizin.uni-leipzig.de
Phone: +49 341 - 97 22117​​

Research

Molecular and physiological analysis of two novel adhesion GPCRs (CG15556/ketchup and CG11318/mayo) in Drosophila melanogaster

Only few aGPCRs are well known and described in Drosophila, thus we re-screened for novel aGPCRs genes and recently discovered CG15556/ketchup and CG11318/mayo. Phylogenetical studies shown that these two new aGPCRs do not have any homolog in vertebrates, therefore they are still orphan with respect to their activation, molecular function or signal transduction. One of the aims of the present project is to test through immunoprecipitation the possible ligands of mayo and through the well stablished heart beat assay test for positive candidates. 

Investigation of adhesion GPCR signaling pathways

In this project we aim to molecularly and pharmacologically characterize the newly identified Drosophila melanogaster ADGRA homolog CG15744/Remoulade. For that purpose, we will use a proteomic/mass spectrometric approach to identify additional interaction partners of Remoulade. Through FRET/BRET assays we will interrogate the Remoulade signaling pathway and study conditions for receptor/co-receptor/ligand assembly and disassembly. Finally, hypotheses on the molecular mechanisms of ADGRA signaling can be readily tested under in vivo conditions by virtue of a Drosophila genomic engineering platform that can rapidly produce allelic Remoulade variants of interest. Collectively, this will allow for a better understanding of how this unusual adhesion GPCR subfamily executes its signaling functions. 

​Study of the NEDCAM disease

This project aims to elucidate the effects of disease-causing gemin5 gene mutations and the pathophysiology of NEDCAM (neurodevelopmental disorder with cerebellar atrophy and motor dysfunction). To address the current lack of animal models for NEDCAM, we plan to generate a complete knock-out of the gemin5 gene in Drosophila melanogaster (in fly also referred to as rigor mortis or rig) using the CRISPR/Cas9. For a better understanding of the disease, we will generate multiple knock-in lines expressing wild type or pathogenic gemin5 variants for further characterization. Our goal is to better understand how the rare disease NEDCAM functions and determine whether the two recessive inherited diseases spinal muscular atrophy (SMA) – well researched and caused by defects in the SMN protein and NEDCAM share a common pathogenic pathway. Our long-term goal is to see if SMN inducing therapies approved to treat SMA patients could be a viable strategy for treating NEDCAM​.

Projects

  • Cell biological and molecular analyses on GAIN domain cleavability of adhesion GPCRs
  • Remoulade signaling pathways
  • Study of the NEDCAM disease ​

Team



Alumni

  • Paul Winter (Bachelor Student)​
  • Genevieve Auger​​ (PhD Candidate, jointly with the Langenhan lab)​
  • Fernando Vieira Contreras (PhD Candidate, jointly with the Langenhan lab)
  • Javier Pereira (Erasmus student)
  • Irene Ginés (Erasmus student)
  • Lena Müller (Bachelor/Master student)​

Publications

(*Equal contribution /​ #Shared correspondence)

Contreras FV*, Auger GM*, Müller L, Richter V, Huetteroth W, Seufert F, Hildebrand PW, Scholz N, Thum AS, Ljaschenko D, Blanco-Redondo B#, Langenhan T#. The adhesion G-protein-coupled receptor mayo/CG11318 controls midgut development in Drosophila. Cell Rep. 2024;43(1):113640. doi:10.1016/j.celrep.2023.113640​

Scholz N*#, Dahse AK*, Kemkemer M, Bormann A, Auger GM, Vieira Contreras F, Ernst LF, Staake H, Körner MB, Buhlan M, Meyer-Mölck A, Chung YK, Blanco-Redondo B, Klose F, Jarboui MA, Ljaschenko D, Bigl M, Langenhan T​# (2023). Molecular sensing of mechano- and ligand-dependent adhesion GPCR dissociation. Nature, 615(7954), 945-953. doi:10.1038/s41586-023-05802-5

Buettner JM*, Sowoidnich L*, Gerstner F, Blanco-Redondo B, Hallermann S, Simon CM (2022). p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models. Front Cell Neurosci, 16, 1038276. doi:10.3389/fncel.2022.1038276

Korobeynikov VA*, Lyashchenko AK*, Blanco-Redondo B*, Jafar-Nejad P, Shneider NA (2022). Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis. Nat Med, 28, 104-116. doi:10.1038/s41591-021-01615-z

Buettner JM*, Sime Longang JKS*, Gerstner F, Apel KS, Blanco-Redondo B, Sowoidnich L, Janzen E, Langenhan T, Wirth B, Simon CM (2021). Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models. iScience, 24, 103376. doi:10.1016/j.isci.2021.103376

Simon CM, Blanco-Redondo B, Buettner JM, Pagiazitis JG, Fletcher EV, Sime Longang JK, Mentis GZ (2021). Chronic Pharmacological Increase of Neuronal Activity Improves Sensory-Motor Dysfunction in Spinal Muscular Atrophy Mice. J Neurosci, 41, 376-389. doi:10.1523/jneurosci.2142-20.2020

Blanco-Redondo B#, Nuwal N, Kneitz S, Nuwal T, Halder P, Liu Y, Ehmann N, Scholz N, Mayer A, Kleber J, Kahne T, Schmitt D, Sadanandappa MK, Funk N, Albertova V, Helfrich-Forster C, Ramaswami M, Hasan G, Kittel RJ, Langenhan T, Gerber B, Buchner E# (2019). Implications of the Sap47 null mutation for synapsin phosphorylation, longevity, climbing proficiency and behavioural plasticity in adult Drosophila. J Exp Biol, 222, 203505.​ doi:10.1242/jeb.203505

Blanco-Redondo B, Langenhan T (2018). Parallel Genomic Engineering of Two Drosophila Genes Using Orthogonal attB/attP Sites. G3 (Bethesda), 8(9), 3109-3118.​ doi:10.1534/g3.118.200565

Blanco Redondo B*, Bunz M*, Halder P*​, Sadanandappa MK, Mühlbauer B, Erwin F, Hofbauer A, Rodrigues V, VijayRaghavan K, Ramaswami M, Rieger D, Wegener C, Förster C, Buchner E (2013). Identification and stuctural characterization of interneurons of the Drosophila brain by monoclonal antibodies of the würzburg hybridoma library. Plos One, 8(9):e75420. doi:10.1371/journal.pone.0075420

Sadanandappa MK, Blanco Redondo B, Michels B, Rodrigues V, Gerber B, VijayRaghavan K, Buchner E, Ramaswami M (2013). Synapsin function in Gaba-ergic interneurons is required for short-term olfactory habituation. J Neurosci, 33(42):16576-85. doi:10.1523/jneurosci.3142-13.2013​

Johannisallee 30, House J
04103 Leipzig
Phone:
+49 341 - 97 22150
Fax:
+49 341 - 97 22159
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