As mentioned in last week’s blog post, many more videos have been uploaded on to BHDSyndrome.org, and this week we would like to highlight our interview with Dr Ferenc Müller, a senior lecturer in Genetics at the University of Birmingham in the United Kingdom.

The Müller laboratory mainly studies transcriptional regulation in zebrafish (Danio rerio), a model organism in which many developmental and physiological processes are conserved throughout vertebrate evolution. In addition, this genetically tractable research model benefits from easy maintenance at high densities in the laboratory, a short generation time, the large numbers of eggs produced year-round by each mating, and the fact that its externally fertilised eggs can develop rapidly as transparent embryos. The latter is especially appealing as it permits the live and direct observation of vertebrate development, which mammalian model organisms cannot provide.

As well as researching the regulation of transcription, Dr Müller and his collaborators also use zebrafish to study the genetic basis of human disease. For example, they have conducted research into several disorders, such as arthrogryposis, renal dysfunction and cholestasis syndrome (Cullinane et al., 2010), autosomal recessive hereditary spastic paraplegia with thin corpus callosum (Southgate et al., 2010) and Warburg micro syndrome (Bem et al., 2011).

Zebrafish models of disorders associated with BHD, such as VHL (van Rooijen et al., 2009), Peutz-Jeghers syndrome (van der Velden et al., 2011) and TSC (Kim et al., 2011), have also shown how useful this system is in defining the pathogenic mechanisms involved in these multi-organ conditions. Therefore, the Müller lab is working on a zebrafish model of BHD syndrome in collaboration with Professor Eamonn Maher, the Chair of Medical Genetics at the University of Birmingham. It is hoped that this model will shed more light on the functions of Folliculin and also be used to test potential new therapies for BHD in the future.

To hear more about Dr Müller’s on-going BHD research, watch our video interview with its accompanying transcript and audio-only file. The following publications may also be of interest and should illustrate the research that is currently being undertaken in this lab:

 

• Bem D, Yoshimura S, Nunes-Bastos R, Bond FC, Kurian MA, Rahman F, Handley MT, Hadzhiev Y, Masood I, Straatman-Iwanowska AA, Cullinane AR, McNeill A, Pasha SS, Kirby GA, Foster K, Ahmed Z, Morton JE, Williams D, Graham JM, Dobyns WB, Burglen L, Ainsworth JR, Gissen P, Müller F, Maher ER, Barr FA, & Aligianis IA (2011). Loss-of-function mutations in RAB18 cause Warburg micro syndrome. American journal of human genetics, 88 (4), 499-507 PMID: 21473985

• Cullinane AR, Straatman-Iwanowska A, Zaucker A, Wakabayashi Y, Bruce CK, Luo G, Rahman F, Gürakan F, Utine E, Ozkan TB, Denecke J, Vukovic J, Di Rocco M, Mandel H, Cangul H, Matthews RP, Thomas SG, Rappoport JZ, Arias IM, Wolburg H, Knisely AS, Kelly DA, Müller F, Maher ER, & Gissen P (2010). Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization. Nature genetics, 42 (4), 303-12 PMID: 20190753

• Gehrig J, Reischl M, Kalmár E, Ferg M, Hadzhiev Y, Zaucker A, Song C, Schindler S, Liebel U, & Müller F (2009). Automated high-throughput mapping of promoter-enhancer interactions in zebrafish embryos. Nature methods, 6 (12), 911-6 PMID: 19898487

• Kim SH, Speirs CK, Solnica-Krezel L, & Ess KC (2011). Zebrafish model of tuberous sclerosis complex reveals cell-autonomous and non-cell-autonomous functions of mutant tuberin. Disease models & mechanisms, 4 (2), 255-67 PMID: 20959633

• Southgate L, Dafou D, Hoyle J, Li N, Kinning E, Critchley P, Németh AH, Talbot K, Bindu PS, Sinha S, Taly AB, Raghavendra S, Müller F, Maher ER, & Trembath RC (2010). Novel SPG11 mutations in Asian kindreds and disruption of spatacsin function in the zebrafish. Neurogenetics, 11 (4), 379-89 PMID: 20390432

• van der Velden YU, Wang L, Zevenhoven J, van Rooijen E, van Lohuizen M, Giles RH, Clevers H, & Haramis AP (2011). The serine-threonine kinase LKB1 is essential for survival under energetic stress in zebrafish. Proceedings of the National Academy of Sciences of the United States of America, 108 (11), 4358-63 PMID: 21368212

• van Rooijen E, Voest EE, Logister I, Korving J, Schwerte T, Schulte-Merker S, Giles RH, & van Eeden FJ (2009). Zebrafish mutants in the von Hippel-Lindau tumor suppressor display a hypoxic response and recapitulate key aspects of Chuvash polycythemia. Blood, 113 (25), 6449-60 PMID: 19304954