Meinrad Busslinger

Last updated
Meinrad Busslinger
Born (1952-07-30) 30 July 1952 (age 72)
Gebenstorf, Switzerland
NationalitySwiss
Alma mater
Known for B cell differentiation
Awards
Scientific career
Fields biochemistry, immunology
Institutions
Thesis  (1981)
Doctoral advisor Max L. Birnstiel
Website www.imp.ac.at/groups/meinrad-busslinger/

Meinrad Busslinger (born 30 July 1952) 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. [1]

Contents

Early life and education

Meinrad Busslinger was born on 30 July 1952 in Gebenstorf, Switzerland. [2] He grew up in the Swiss town of Zug, where he obtained his grammar school education. From 1972 to 1976, he studied natural sciences at the Swiss Federal Institute of Technology (ETH 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

Related Research Articles

<span class="mw-page-title-main">Haematopoiesis</span> Formation of blood cellular components

Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten billion to a hundred billion new blood cells are produced per day, in order to maintain steady state levels in the peripheral circulation.

<span class="mw-page-title-main">Transcription factor</span> Protein that regulates the rate of DNA transcription

In molecular biology, a transcription factor (TF) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are approximately 1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome.

<span class="mw-page-title-main">Homeobox</span> DNA pattern affecting anatomy development

A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. Mutations in a homeobox may change large-scale anatomical features of the full-grown organism.

<span class="mw-page-title-main">Pax genes</span> Family of transcription factors

In evolutionary developmental biology, Paired box (Pax) genes are a family of genes coding for tissue specific transcription factors containing an N-terminal paired domain and usually a partial, or in the case of four family members, a complete homeodomain to the C-terminus. An octapeptide as well as a Pro-Ser-Thr-rich C terminus may also be present. Pax proteins are important in early animal development for the specification of specific tissues, as well as during epimorphic limb regeneration in animals capable of such.

<span class="mw-page-title-main">PAX6</span> Protein-coding gene in humans

Paired box protein Pax-6, also known as aniridia type II protein (AN2) or oculorhombin, is a protein that in humans is encoded by the PAX6 gene.

<span class="mw-page-title-main">PAX3</span> Paired box gene 3

The PAX3 gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse Pax3 are present in a subfamily along with the highly homologous human PAX7 and mouse Pax7 genes. The human PAX3 gene is located in the 2q36.1 chromosomal region, and contains 10 exons within a 100 kb region.

<span class="mw-page-title-main">Microphthalmia-associated transcription factor</span> Mammalian protein found in humans

Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the MITF gene.

<span class="mw-page-title-main">CD19</span> Biomarker for B cell lineage

B-lymphocyte antigen CD19, also known as CD19 molecule, B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12 and CVID3 is a transmembrane protein that in humans is encoded by the gene CD19. In humans, CD19 is expressed in all B lineage cells. Contrary to some early doubts, human plasma cells do express CD19. CD19 plays two major roles in human B cells: on the one hand, it acts as an adaptor protein to recruit cytoplasmic signaling proteins to the membrane; on the other, it works within the CD19/CD21 complex to decrease the threshold for B cell receptor signaling pathways. Due to its presence on all B cells, it is a biomarker for B lymphocyte development, lymphoma diagnosis and can be utilized as a target for leukemia immunotherapies.

<span class="mw-page-title-main">PAX2</span> Protein-coding gene in humans

Paired box gene 2, also known as Pax-2, is a protein which in humans is encoded by the PAX2 gene.

<span class="mw-page-title-main">PAX8</span> Mammalian protein found in humans

Paired box gene 8, also known as PAX8, is a protein which in humans is encoded by the PAX8 gene.

<span class="mw-page-title-main">PAX5</span> Protein-coding gene in humans

Paired box protein Pax-5 is a protein that in humans is encoded by the PAX5 gene.

<span class="mw-page-title-main">PAX4</span> Protein-coding gene in humans

Paired box gene 4, also known as PAX4, is a protein which in humans is encoded by the PAX4 gene.

<span class="mw-page-title-main">PAX7</span> Paired box transcription factor protein

Paired box protein Pax-7 is a protein that in humans is encoded by the PAX7 gene.

<span class="mw-page-title-main">EBF1</span> Protein-coding gene in the species Homo sapiens

Transcription factor COE1 is a protein that in humans is encoded by the EBF1 gene. EBF1 stands for Early B-Cell Factor 1.

<span class="mw-page-title-main">PITX1</span> Protein-coding gene in humans

Paired-like homeodomain 1 is a protein that in humans is encoded by the PITX1 gene.

<span class="mw-page-title-main">TLE4</span> Protein-coding gene in the species Homo sapiens

Transducin-like enhancer protein 4 is a protein that in humans is encoded by the TLE4 gene.

<span class="mw-page-title-main">Research Institute of Molecular Pathology</span>

The Research Institute of Molecular Pathology (IMP) is a biomedical research center, which conducts curiosity-driven basic research in the molecular life sciences.

<span class="mw-page-title-main">MYF5</span> Protein-coding gene in the species Homo sapiens

Myogenic factor 5 is a protein that in humans is encoded by the MYF5 gene. It is a protein with a key role in regulating muscle differentiation or myogenesis, specifically the development of skeletal muscle. Myf5 belongs to a family of proteins known as myogenic regulatory factors (MRFs). These basic helix loop helix transcription factors act sequentially in myogenic differentiation. MRF family members include Myf5, MyoD (Myf3), myogenin, and MRF4 (Myf6). This transcription factor is the earliest of all MRFs to be expressed in the embryo, where it is only markedly expressed for a few days. It functions during that time to commit myogenic precursor cells to become skeletal muscle. In fact, its expression in proliferating myoblasts has led to its classification as a determination factor. Furthermore, Myf5 is a master regulator of muscle development, possessing the ability to induce a muscle phenotype upon its forced expression in fibroblastic cells.

Margaret Buckingham, is a British developmental biologist working in the fields of myogenesis and cardiogenesis. She is an honorary professor at the Pasteur Institute in Paris and emeritus director in the Centre national de la recherche scientifique (CNRS). She is a member of the European Molecular Biology Organization, the Academia Europaea and the French Academy of Sciences.

Alexander Stark is a biochemist and computational biologist working on the regulation of gene expression in development. He is a senior scientist at the Research Institute of Molecular Pathology (IMP) at the Vienna Biocenter and adjunct professor of the Medical University of Vienna.

References

  1. ↑ "Meinrad Busslinger's lab at the IMP" . Retrieved 2019-01-08.
  2. ↑ "Curriculum Vitae – Meinrad Busslinger" (PDF). 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.
  23. ↑ "Preis der Stadt Wien" . Retrieved 2021-07-15.
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