Meinrad Busslinger
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Meinrad Busslinger (born 30 July 1952 in
Gebenstorf Gebenstorf is a municipality in the district of Baden in the canton of Aargau in Switzerland. History Gebenstorf is first mentioned in 1247 as ''Gobistorf''. From 1415 until 1798 it was a township in the county of Baden. The historical border ...
,
Switzerland ). Swiss law does not designate a ''capital'' as such, but the federal parliament and government are installed in Bern, while other federal institutions, such as the federal courts, are in other cities (Bellinzona, Lausanne, Luzern, Neuchâtel ...
) is a
biochemist Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemical transformations in living organisms. Biochemists study DNA, proteins and Cell (biology), cell parts. The word "biochemist" is a portmanteau of ...
and immunologist, renown for his work on
B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
. He is a Senior Scientist and Scientific Deputy Director of the
Research Institute of Molecular Pathology The Research Institute of Molecular Pathology (IMP) is a biomedical research center, which conducts curiosity-driven basic research in the molecular life sciences. The IMP is located at the Vienna Biocenter in Vienna, Austria. The institute emplo ...
(IMP) in
Vienna en, Viennese , iso_code = AT-9 , registration_plate = W , postal_code_type = Postal code , postal_code = , timezone = CET , utc_offset = +1 , timezone_DST ...
,
Austria Austria, , bar, Östareich officially the Republic of Austria, is a country in the southern part of Central Europe, lying in the Eastern Alps. It is a federation of nine states, one of which is the capital, Vienna, the most populous ...
.


Early life and education

Meinrad Busslinger grew up in the Swiss town of
Zug , neighboring_municipalities = Cham, Baar, Walchwil, Steinhausen, Unterägeri , twintowns = Fürstenfeld (Austria), Kalesija (Bosnia-Herzegowina) Zug (Standard German: , Alemannic German: ; french: Zoug it, Zugo r ...
, near Zurich, where he obtained his grammar school education. From 1972 to 1976, he studied natural sciences at the
Swiss Federal Institute of Technology The Swiss Federal Institutes of Technology are two institutes of higher education in Switzerland (part of the ETH Domain): * Swiss Federal Institute of Technology in Lausanne Swiss may refer to: * the adjectival form of Switzerland *Swiss people ...
(ETH) in Zurich, where he majored in biochemistry. During his PhD studies (1976-1981), Busslinger discovered important regulatory elements involved in the
transcriptional control In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from alt ...
of
gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
by investigating the
regulation Regulation is the management of complex systems according to a set of rules and trends. In systems theory, these types of rules exist in various fields of biology and society, but the term has slightly different meanings according to context. For ...
of
sea urchin Sea urchins () are spiny, globular echinoderms in the class Echinoidea. About 950 species of sea urchin live on the seabed of every ocean and inhabit every depth zone from the intertidal seashore down to . The spherical, hard shells (tests) of ...
histone genes. He performed his PhD work under the supervision of
Max L. Birnstiel Max Luciano Birnstiel (12 July 1933 – 15 November 2014) was a Swiss molecular biologist who held a number of positions in scientific leadership in Europe, including the chair of the Institute of Molecular Biology at the University of Zurich from ...
at the
University of Zurich The University of Zürich (UZH, german: Universität Zürich) is a public research university located in the city of Zürich, Switzerland. It is the largest university in Switzerland, with its 28,000 enrolled students. It was founded in 1833 f ...
, from where he received a PhD degree in molecular biology in 1981.


Career and research

In 1981, Busslinger joined the lab of Richard A. Flavell at the
MRC MRC may refer to Government * Medical Research Council (United Kingdom) * Medical Reserve Corps, a US network of volunteer organizations * Municipalité régionale de comté (regional county municipality), Quebec, Canada * Military Revolutionar ...
Institute Mill Hill in
London London is the capital and largest city of England and the United Kingdom, with a population of just under 9 million. It stands on the River Thames in south-east England at the head of a estuary down to the North Sea, and has been a majo ...
as a postdoctoral fellow. There, he discovered that a single nucleotide mutation in the first
intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...
of the β-globin gene causes β+-thalassemia and that
DNA methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
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 In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) 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 fu ...
(TSAP) as an essential regulator of these genes, which later turned out to be a member of the Paired box (Pax)-containing transcription factor family. In 1987, Max Birnstiel recruited Busslinger to join the newly founded
Research Institute of Molecular Pathology The Research Institute of Molecular Pathology (IMP) is a biomedical research center, which conducts curiosity-driven basic research in the molecular life sciences. The IMP is located at the Vienna Biocenter in Vienna, Austria. The institute emplo ...
(IMP) in Vienna, Austria, as one of the first Senior Scientists. In 1996, Busslinger was appointed Professor at the
University of Vienna The University of Vienna (german: Universität Wien) is a public research university located in Vienna, Austria. It was founded by Duke Rudolph IV in 1365 and is the oldest university in the German-speaking world. With its long and rich histor ...
. In 2007, he became the IMP's Director of Academic Affairs and, in 2013, Scientific Deputy Director. At the IMP, Busslinger changed his research focus from sea urchin
embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
to
B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
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 Paired box protein Pax-5 is a protein that in humans is encoded by the ''PAX5'' gene. Function The PAX5 gene is a member of the paired box (PAX) family of transcription factors. The central feature of this gene family is a novel, highly cons ...
, 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 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 and to function as an important
tumor suppressor A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...
or oncoprotein in B cell leukemia. In addition to Pax5, the Busslinger group investigated the role of other important transcription factors, such as E2A, EBF1, 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 The immunoglobulin heavy chain (IgH) is the large polypeptide subunit of an antibody (immunoglobulin). In human genome, the IgH gene loci are on chromosome 14. A typical antibody is composed of two immunoglobulin (Ig) heavy chains and two Ig li ...
(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 as a critical regulator of IgH locus contraction that facilitates chromatin loop extrusion across the entire locus. He is a member of the Editorial Board for ''Immunity''.


Awards and honours

*1981 Postdoctoral fellowship (
Swiss National Science Foundation The Swiss National Science Foundation (SNSF, German: ''Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung'', SNF; French: ''Fonds national suisse de la recherche scientifique'', FNS; Italian: ''Fondo nazionale svizzero ...
) *1990 Member of the
European Molecular Biology Organization The European Molecular Biology Organization (EMBO) is a professional, non-profit organization of more than 1,800 life scientists. Its goal is to promote research in life science and enable international exchange between scientists. It co-funds cour ...
(EMBO) *2000 Member of the
Academia Europaea The Academia Europaea is a pan-European Academy of Humanities, Letters, Law, and Sciences. The Academia was founded in 1988 as a functioning Europe-wide Academy that encompasses all fields of scholarly inquiry. It acts as co-ordinator of Europea ...
*2001
Wittgenstein Award The Wittgenstein Award (german: Wittgenstein-Preis) is an Austrian science award supporting the notion that "scientists should be guaranteed the greatest possible freedom and flexibility in the performance of their research." The prize money of up ...
*2005 Corresponding member of the Austrian Academy of Sciences *2009 Full member of the Austrian Academy of Sciences *2012
European Research Council The European Research Council (ERC) is a public body for funding of scientific and technological research conducted within the European Union (EU). Established by the European Commission in 2007, the ERC is composed of an independent Scientific ...
(ERC) Advanced Grant *2010 Virchow Medal, Medical Faculty,
University of Würzburg The Julius Maximilian University of Würzburg (also referred to as the University of Würzburg, in German ''Julius-Maximilians-Universität Würzburg'') is a public research university in Würzburg, Germany. The University of Würzburg is one of ...
*2015 Honorary member of the Swiss Society for Allergology and Immunology *2017 European Research Council (ERC) Advanced Grant *2020 Preis der Stadt Wien für Naturwissenschaften


References

{{DEFAULTSORT:Busslinger, Meinrad Members of the European Molecular Biology Organization Living people 1952 births 21st-century biochemists European Research Council grantees