Michael Rossmann
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Michael G. Rossmann (30 July 1930 – 14 May 2019) was a
German-American German Americans (german: Deutschamerikaner, ) are Americans who have full or partial German ancestry. With an estimated size of approximately 43 million in 2019, German Americans are the largest of the self-reported ancestry groups by the Unite ...
physicist, microbiologist, and Hanley Distinguished Professor of Biological Sciences at
Purdue University Purdue University is a public land-grant research university in West Lafayette, Indiana, and the flagship campus of the Purdue University system. The university was founded in 1869 after Lafayette businessman John Purdue donated land and mone ...
who led a team of researchers to be the first to map the structure of a human common cold virus to an atomic level. He also discovered the
Rossmann fold The Rossmann fold is a tertiary fold found in proteins that bind nucleotides, such as enzyme cofactors FAD, NAD+, and NADP+. This fold is composed of alternating beta strands and alpha helical segments where the beta strands are hydrogen bonde ...
protein motif. His most well recognised contribution to structural biology is the development of a phasing technique named molecular replacement, which has led to about three quarters of depositions in the
Protein Data Bank The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, ...
.


Education

Born in
Frankfurt Frankfurt, officially Frankfurt am Main (; Hessian: , " Frank ford on the Main"), is the most populous city in the German state of Hesse. Its 791,000 inhabitants as of 2022 make it the fifth-most populous city in Germany. Located on it ...
, Germany, Rossmann studied physics and mathematics at the
University of London The University of London (UoL; abbreviated as Lond or more rarely Londin in post-nominals) is a federal public research university located in London, England, United Kingdom. The university was established by royal charter in 1836 as a degree ...
, where he received BSc and MSc degrees. He moved to
Glasgow Glasgow ( ; sco, Glesca or ; gd, Glaschu ) is the most populous city in Scotland and the fourth-most populous city in the United Kingdom, as well as being the 27th largest city by population in Europe. In 2020, it had an estimated popul ...
in 1953 where he taught physics in the technical college and received his Ph.D. in chemical crystallography in 1956. He attributes his initial interest in crystallography to
Kathleen Lonsdale Dame Kathleen Lonsdale ( Yardley; 28 January 1903 – 1 April 1971) was an Irish-born British pacifist, prison reformer and crystallographer. She proved, in 1929, that the benzene ring is flat by using X-ray diffraction methods to elucidate t ...
, whom he heard speak as a schoolboy. Rossmann began his career as a crystallographer when he became a student of J. Monteath Robertson at the
University of Glasgow , image = UofG Coat of Arms.png , image_size = 150px , caption = Coat of arms Flag , latin_name = Universitas Glasguensis , motto = la, Via, Veritas, Vita , ...
. The title of his thesis was "A Study of Some Organic Crystal Structures". In 1956 he and his family moved to the
University of Minnesota The University of Minnesota, formally the University of Minnesota, Twin Cities, (UMN Twin Cities, the U of M, or Minnesota) is a public land-grant research university in the Twin Cities of Minneapolis and Saint Paul, Minnesota, United States. ...
, where he worked for two years as a post-doctoral fellow with Professor William N. Lipscomb, Jr., publishing on the structure of an Iresin Diester and a
terpenoid The terpenoids, also known as isoprenoids, are a class of naturally occurring organic chemicals derived from the 5-carbon compound isoprene and its derivatives called terpenes, diterpenes, etc. While sometimes used interchangeably with "terpenes" ...
, and writing computer programs for analysing structures.


Career

Rossmann returned to the UK and to the
University of Cambridge The University of Cambridge is a public collegiate research university in Cambridge, England. Founded in 1209 and granted a royal charter by Henry III in 1231, Cambridge is the world's third oldest surviving university and one of its most pr ...
in 1958, where he worked with
Max Perutz Max Ferdinand Perutz (19 May 1914 – 6 February 2002) was an Austrian-born British molecular biologist, who shared the 1962 Nobel Prize for Chemistry with John Kendrew, for their studies of the structures of haemoglobin and myoglobin. He went ...
on the structure of
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
as a research associate at the MRC
Laboratory of Molecular Biology The Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) is a research institute in Cambridge, England, involved in the revolution in molecular biology which occurred in the 1950–60s. Since then it has remained a major medical r ...
. In 1964 Rossmann joined the faculty of the Department of Biological Sciences at Purdue University as an associate professor. He directed the Purdue
X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
laboratory. He became full professor in 1967 and from 1978 held the chair of Hanley Distinguished Professor of Biological Sciences at the university. He also held a joint appointment in the department of biochemistry and adjunct positions in
Cornell University Cornell University is a private statutory land-grant research university based in Ithaca, New York. It is a member of the Ivy League. Founded in 1865 by Ezra Cornell and Andrew Dickson White, Cornell was founded with the intention to tea ...
's Division of Biological Sciences and in
Indiana University Indiana University (IU) is a system of public universities in the U.S. state of Indiana. Campuses Indiana University has two core campuses, five regional campuses, and two regional centers under the administration of IUPUI. *Indiana Universi ...
's school of medicine. In 1970 his laboratory found the structure of dogfish
lactate dehydrogenase Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from one ...
, one of the largest early proteins to be solved. In 1973 his group found the structure of Glyceraldehyde 3-phosphate dehydrogenase, and Rossmann immediately realized that the binding site for the NAD+ was very similar to the one in the lactate dehydrogenase. This is now called the
Rossmann fold The Rossmann fold is a tertiary fold found in proteins that bind nucleotides, such as enzyme cofactors FAD, NAD+, and NADP+. This fold is composed of alternating beta strands and alpha helical segments where the beta strands are hydrogen bonde ...
. It is found in
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s (such as
dehydrogenase A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as ...
s or kinases) that bind molecules such as ATP or NAD+/NADH. Rossmann then turned to viruses, spending a sabbatical in 1971 with Bror Strandberg in
Uppsala Uppsala (, or all ending in , ; archaically spelled ''Upsala'') is the county seat of Uppsala County and the fourth-largest city in Sweden, after Stockholm, Gothenburg, and Malmö. It had 177,074 inhabitants in 2019. Located north of the c ...
, Sweden, working on the structure of the satellite tobacco necrosis virus. From 1972 to 1980 Rossmann and his team worked on the southern bean mosaic virus. This required developing new software and adapting existing software for Fourier transforms. It was found that this virus had a similar " jelly roll fold" to that found previously in the tomato bushy stunt virus, which at the time was a surprise. In the early 1980s Rossmann began working on
picornavirus Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30 nm ...
es, and chose HRV14, one of the viruses that cause the common cold. Part of the problem was that it was very difficult at the time to produce milligram quantities of an animal virus, as needed for the X-ray crystallography. Rossmann pushed for the purchase by Purdue of a Cyber 205 supercomputer, capable of delivering hundreds of megaflops. After vectorizing the computer programs, calculations that had taken six weeks with the southern bean mosaic virus now took, for HRV14, only a fraction of a day. In 1985, he published his team's mapping in the journal
Nature Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans are ...
. The breakthrough nature of this result was such that the
National Science Foundation The National Science Foundation (NSF) is an independent agency of the United States government that supports fundamental research and education in all the non-medical fields of science and engineering. Its medical counterpart is the National ...
, which provided partial funding for the research, saw fit to organize a press conference, and the news travelled in the general press. This work laid the foundation for a molecular understanding of cell entry of
enteroviruses ''Enterovirus'' is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal). Serologic ...
and for the development of capsid-binding inhibitors against a broad range of
enteroviruses ''Enterovirus'' is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal). Serologic ...
. After the success with the first cold virus, work was done on
alphavirus ''Alphavirus'' is a genus of RNA viruses, the sole genus in the ''Togaviridae'' family. Alphaviruses belong to group IV of the Baltimore classification of viruses, with a positive-sense, single-stranded RNA genome. There are 32 alphaviruses ...
es and flaviviruses. Using cryo-electron microscopy, in 2016 his lab reported the first known structure of the
Zika virus ''Zika virus'' (ZIKV; pronounced or ) is a member of the virus family ''Flaviviridae''. It is spread by daytime-active '' Aedes'' mosquitoes, such as '' A. aegypti'' and '' A. albopictus''. Its name comes from the Ziika Forest of Uganda, w ...
, responsible for a severe epidemic at the time. This work was made possible by more than one decade of studies on related mosquito borne flaviviruses, including dengue virus, using a combination of cryo-electron microscopy and
X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
. Rossmann also had a long-term interest in complicated viral machines. These are exemplified by
bacteriophage T4 Escherichia virus T4 is a species of bacteriophages that infect ''Escherichia coli'' bacteria. It is a double-stranded DNA virus in the subfamily '' Tevenvirinae'' from the family Myoviridae. T4 is capable of undergoing only a lytic lifecycle ...
and nucleocytoplasmic large DNA viruses, also referred to as giant viruses. The determination of an atomic structure of Paramecium bursaria chlorella virus 1 that infects algae has opened up new possibilities for studying giant viruses at the atomic level.


Life and hobbies

Rossmann was an avid hiker and sailboat enthusiast, winning M-16 Scow races on Indiana lakes. He was very energetic, which sometimes caused difficulties for his team members. Rossmann's wife, Audrey, was a potter and artist. They had three children, Martin, Alice, and Heather. Audrey died in 2009. When diagnosed with cancer, Rossmann moved into a retirement home, where he met and later married a staff member in charge of welcoming and hospitality, Karen Bogan. He was working on papers and grant proposals until shortly before his death. Rossmann died on 14 May 2019. Purdue president (and former Indiana governor)
Mitch Daniels Mitchell Elias Daniels Jr. (born April 7, 1949) is an American academic administrator, businessman, author, and retired politician. A Republican, Daniels served as the 49th governor of Indiana from 2005 to 2013. Since 2013, Daniels has been pr ...
said of him, "Still vital, still curious, still in his lab at age 88, his was a life as rich in personal example as it was in scientific achievement."


Rossmann supercomputer

The Rossmann cluster is named for Michael Rossmann, Purdue's Hanley Distinguished Professor of Biological Sciences, who is a pioneer in employing high-performance computing in research to reveal the structure of viruses and their component protein molecules. Calculating electron density structure from X-ray crystallography results by Rossmann's team had long been one of the larger tasks carried out on Purdue's computing systems.


Awards and honors

Among other honors, Michael Rossmann was elected Fellow of the
American Academy of Arts and Sciences The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, a ...
in 1978, Member of the National Academy of Sciences in 1984, Foreign Member of the
Royal Society of London The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
in 1996, and Fellow of the American Association for the Advancement of Science in 1999. In 1990, he was awarded Louisa Gross Horwitz Prize from
Columbia University Columbia University (also known as Columbia, and officially as Columbia University in the City of New York) is a private research university in New York City. Established in 1754 as King's College on the grounds of Trinity Church in Manhatt ...
. He was awarded honorary doctorates by
Uppsala University Uppsala University ( sv, Uppsala universitet) is a public research university in Uppsala, Sweden. Founded in 1477, it is the oldest university in Sweden and the Nordic countries still in operation. The university rose to significance during ...
, Sweden (1983); the
University of Strasbourg The University of Strasbourg (french: Université de Strasbourg, Unistra) is a public research university located in Strasbourg, Alsace, France, with over 52,000 students and 3,300 researchers. The French university traces its history to the ea ...
, France; Vrije Universiteit Brussel, Belgium;
University of Glasgow , image = UofG Coat of Arms.png , image_size = 150px , caption = Coat of arms Flag , latin_name = Universitas Glasguensis , motto = la, Via, Veritas, Vita , ...
, Scotland; University of York, England; Institut Armand-Frappier, University of Québec, Canada. He was awarded the
Gregori Aminoff Prize The Gregori Aminoff Prize is an international prize awarded since 1979 by the Royal Swedish Academy of Sciences in the field of crystallography, rewarding "a documented, individual contribution in the field of crystallography, including areas conce ...
in 1994 and the Paul Ehrlich and Ludwig Darmstaedter Prize in 2001. His own employer awarded him with the Purdue University Medal of Honor in 1995. In 2016, he was awarded the Raymond and Beverly Sackler International Prize in Biophysics for pioneering contributions to high-resolution diffraction analysis of atomic structures of proteins and viruses.


References

{{DEFAULTSORT:Rossmann, Michael 2019 deaths 1930 births Purdue University faculty Scientists from Frankfurt Alumni of the University of Glasgow 21st-century American physicists Foreign Members of the Royal Society American microbiologists German emigrants to the United States Members of the United States National Academy of Sciences Foreign Fellows of the Indian National Science Academy People from Hesse-Nassau American biophysicists