Meinrad Busslinger

Meinrad Busslinger (born 30 July 1952 in Gebenstorf, Switzerland[1]) is a biochemist and immunologist, renown for his work on B cells. He is a Senior Scientist and Scientific Deputy Director of the Research Institute of Molecular Pathology (IMP) in Vienna, Austria.[2]

Meinrad Busslinger
Born
Meinrad Busslinger

(1952-07-30) 30 July 1952
Gebenstorf
NationalitySwiss
Alma mater
Known for B cell differentiation
Awards
Scientific career
Fieldsbiochemistry, immunology
Institutions
Thesis (1981)
Doctoral advisorMax L. Birnstiel
Websitewww.imp.ac.at/groups/meinrad-busslinger/

Early life and education

Meinrad Busslinger grew up in the Swiss town of Zug, near Zurich, where he obtained his grammar school education. From 1972 to 1976, he studied natural sciences at the Swiss Federal Institute of Technology (ETH) in Zurich, where he majored in biochemistry.

During his PhD studies (1976-1981), Busslinger discovered important regulatory elements involved in the transcriptional control of gene expression by investigating the regulation of sea urchin histone genes. He performed his PhD work under the supervision of Max L. Birnstiel at the University of Zurich, from where he received a PhD degree in molecular biology in 1981.[3]

Career and research

In 1981, Busslinger joined the lab of Richard A. Flavell at the MRC Institute Mill Hill in London as a postdoctoral fellow. There, he discovered that a single nucleotide mutation in the first intron of the β-globin gene causes β+-thalassemia and that DNA methylation of promoter sequences prevents gene transcription.

In 1983, Busslinger became a Group Leader at the Institute of Molecular Biology II of the University of Zurich. Here, he discovered a new set of histone genes of the sea urchin and identified a tissue-specific transcription factor (TSAP) as an essential regulator of these genes,[4] which later turned out to be a member of the Paired box (Pax)-containing transcription factor family.[5]

In 1987, Max Birnstiel recruited Busslinger to join the newly founded Research Institute of Molecular Pathology (IMP) in Vienna, Austria, as one of the first Senior Scientists. In 1996, Busslinger was appointed Professor at the University of Vienna. In 2007, he became the IMP's Director of Academic Affairs and, in 2013, Scientific Deputy Director.[6] At the IMP, Busslinger changed his research focus from sea urchin embryogenesis to B cell immunology, which was promoted by the identification of a B-cell-specific transcription factor as a mammalian homologue of the sea urchin regulator TSAP. Protein purification and sequencing identified the B-cell-specific transcription factor as Pax5,[7] and gene inactivation in the mouse defined Pax5 an essential regulator of B cell development. In 1999, Busslinger and his lab described the first molecular definition of a lineage commitment process by identifying Pax5 as the B cell lineage commitment factor that restricts the developmental options of early lymphoid progenitors to the B cell pathway[8] by repressing lineage-inappropriate genes and that simultaneously promotes B cell development by activating B-cell-specific genes. To date, Pax5 is known to function as a guardian of B cell identity for early to late B cell development[9] and to function as an important tumor suppressor or oncoprotein in B cell leukemia.[10] In addition to Pax5, the Busslinger group investigated the role of other important transcription factors, such as E2A,[11] EBF1,[12] Ikaros, and Blimp1, in regulating distinct aspects of B cell development and immunity.

Busslinger also contributed to the current knowledge of how the large locus encoding the immunoglobulin heavy chain (IgH) protein undergoes spatial contraction by looping in early B cell development. This long-range looping induces the juxtaposition of Variable (V) gene segments next to Diversity (D) gene segments, which facilitates V-to-DJ recombination to generate a functional IgH gene. Busslinger identified Pax5[13] as a critical regulator of IgH locus contraction that facilitates chromatin loop extrusion across the entire locus.[14]

He is a member of the Editorial Board for Immunity.

Awards and honours

References
  1. "Curriculum Vitae – Meinrad Busslinger" (PDF). Retrieved 2019-01-08.
  2. "Meinrad Busslinger's lab at the IMP". Retrieved 2019-01-08.
  3. "Curriculum Vitae – Meinrad Busslinger" (PDF). Retrieved 2019-01-08.
  4. "Developmental and tissue-specific regulation of a novel transcription factor of the sea urchin". Retrieved 2019-01-08.
  5. Czerny, Thomas; Bouchard, Maxime; Kozmik, Zbynek; Busslinger, Meinrad (1997). "The characterization of novel Pax genes of the sea urchin and Drosophila reveal an ancient evolutionary origin of the Pax2/5/8 subfamily". Mechanisms of Development. 67 (2): 179–192. doi:10.1016/S0925-4773(97)00119-6. PMID 9392515. S2CID 14803680.
  6. "IMP Management". Retrieved 2019-01-08.
  7. "Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis". Retrieved 2019-01-08.
  8. "Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature. 1999. 401: 556–562". Retrieved 2019-01-08.
  9. "Pax5/BSAP Maintains the Identity of B Cells in Late B Lymphopoiesis". Retrieved 2019-01-08.
  10. "Molecular role of the PAX5‐ETV6 oncoprotein in promoting B‐cell acute lymphoblastic leukemia". Retrieved 2019-01-08.
  11. "Molecular functions of the transcription factors E2A and E2-2 in controlling germinal center B cell and plasma cell development". Retrieved 2019-01-08.
  12. "Essential role of EBF1 in the generation and function of distinct mature B cell types". Retrieved 2019-01-08.
  13. "Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene". Retrieved 2019-01-08.
  14. "Flexible Long-Range Loops in the VH Gene Region of the Igh Locus Facilitate the Generation of a Diverse Antibody Repertoire". Retrieved 2019-01-08.
  15. "EMBO member database". Retrieved 2019-01-08.
  16. "Member profile Academia Europaea". Retrieved 2019-01-08.
  17. "START- und Wittgenstein-Preise 2001 verliehen (news report in German)". Retrieved 2019-01-08.
  18. "Member directory, Austrian Academy of Sciences". Retrieved 2019-01-08.
  19. "ERC Grant data base". Retrieved 2019-01-08.
  20. "Meeting Report, European Journal of Immunology". Retrieved 2019-01-08.
  21. "ERC Grant data base". Retrieved 2019-01-08.
  22. "Zwei hochdotierte EU-Förderpreise für IMP-Forscher (German)". Retrieved 2019-01-08.
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