Jump to content

Boris Rotman: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
Undid revision 866979504 by 71.223.43.70 (talk) restore tags - see talk page
Expansion
Line 1: Line 1:
{{Multiple issues|{{BLP sources|date=October 2018}}{{original research|date=October 2018}}}}

{{Infobox scientist
{{Infobox scientist
| name =
| name = Marcos Boris Rotman
| image = Rotman27592652.jpg
| image = Rotman27592652.jpg
| alt =
| alt =
| caption = Boris Rotman, 2011
| caption = Boris Rotman, 2011
| birth_date = {{birth year and age|1924}}
| birth_date = {{birth year and age|1924}}
| birth_place = Buenos Aires, Argentina
| birth_place = Buenos Aires, Argentina
| death_date = <!-- {{Death date and age|YYYY|MM|DD|YYYY|MM|DD}} (death date then birth date) -->
| death_date = <!-- {{Death date and age|YYYY|MM|DD|YYYY|MM|DD}} (death date then birth date) -->
| death_place =
| death_place =
| resting_place =
| resting_place =
| resting_place_coordinates = <!--
| resting_place_coordinates = <!-- {{Coord|LAT|LONG|type:landmark|display=inline,title}} -->
| other_names =
{{Coord|LAT|LONG|type:landmark|display=inline,title}} -->
| other_names =
| residence =
⚫
| citizenship = USA
| residence =
⚫
| nationality =
⚫
| citizenship = USA
⚫
| fields = [[Biochemistry]]<br />[[Molecular biology]]
⚫
| nationality =
⚫
| workplaces = [[Brown University]]<br />[[Stanford Medical School]]<br />[[Syntex Institute for Molecular Biology, Stanford]]<br />Escuela de Medicina, [[Universidad de Chile]]<br />[[Karolinska Institute]]<br />[[Weizmann Institute of Science]] – Dept. of Chemical Immunology
⚫
| fields = [[Biochemistry]]<br />[[Molecular biology]]
⚫
| alma_mater = [[University of Illinois]] <small>(PhD, 1952)</small><br />[[Universidad Tecnica Federico Santa Maria]] <small>(M.S., 1948)</small>
⚫
| workplaces = [[Brown University]]<br />[[Stanford Medical School]]<br />[[Syntex Institute for Molecular Biology, Stanford]]<br />Escuela de Medicina, [[Universidad de Chile]]<br />[[Karolinska Institute]]<br />[[Weizmann Institute of Science]] - Dept. of Chemical Immunology
⚫
| thesis_title = A heritable conversion of phenotype in yeast.
⚫
| alma_mater = [[University of Illinois]] <small>(PhD, 1952)</small><br />[[Universidad Tecnica Federico Santa Maria]] <small>(M.S., 1948)</small>
⚫
| thesis_url =
⚫
| thesis_title = A heritable conversion of phenotype in yeast.
⚫
| thesis_year = 1952
⚫
| thesis_url =
⚫
| doctoral_advisor = [[Salvador Luria]] and [[Sol Spiegelman]]
⚫
| thesis_year = 1952
⚫
| doctoral_advisor = [[Salvador Luria]] and [[Sol Spiegelman]]
| academic_advisors = [[Joshua Lederberg]]
| academic_advisors = [[Joshua Lederberg]]
| doctoral_students =
| doctoral_students =
| notable_students =
| notable_students =
| known_for = First [[Single molecule experiment]] in [[biology]]
| known_for = First [[single molecule experiment]] in [[biology]]
| author_abbrev_bot =
| author_abbrev_bot =
| author_abbrev_zoo =
| author_abbrev_zoo =
| influences = [[Salvador Luria]]
| influences = [[Salvador Luria]]
| influenced =
| influenced =
| awards = [[State of Rhode Island Governor's Award for Scientific Achievement]] <small>(1990)</small>
| awards = State of Rhode Island Governor's Award for Scientific Achievement <small>(1990)</small>
| signature = <!--(filename only)-->
| signature = <!--(filename only)-->
| signature_alt =
| signature_alt =
| website = <!-- {{URL|www.bcrbiotech.com}} -->
| website = <!-- {{URL|www.bcrbiotech.com}} -->
| footnotes =
| footnotes =
| spouse = Rosario Guzman-Rotman m 1993
| spouse = Rosario Guzman-Rotman {{small|(married 1993)}}
| children = Jessica R. Yates
| children = Jessica R. Yates
}}
}}


'''Marcos Boris Rotman''' (born 1924), is an American [[immunologist]]–[[molecular biologist]] and professor [[emeritus]] of [[Medical Science]] at [[Alpert Medical School]] of [[Brown University]].<ref>{{cite web |title=Brown University |url=http://www.brown.edu/Faculty/Retirement/people/Emeriti.html |accessdate=10 October 2018}}</ref> He is widely recognized for performing the first [[single molecule experiment]]s in biology.<ref name="Lord Lee Moerner pp. 2192–2203">{{cite journal |last=Lord |first=Samuel J. |last2=Lee |first2=Hsiao-lu D. |last3=Moerner |first3=W. E. |title=Single-Molecule Spectroscopy and Imaging of Biomolecules in Living Cells |journal=Analytical Chemistry |publisher=American Chemical Society (ACS) |volume=82 |issue=6 |date=15 March 2010 |issn=0003-2700 |doi=10.1021/ac9024889 |pages=2192–2203}}</ref><ref name="Knight 2011 pp. 1–9">{{cite book |last=Knight |first=Alex E. |title=Single Molecule Enzymology |chapter=Single Enzyme Studies: A Historical Perspective |publisher=Humana Press |publication-place=Totowa, NJ |year=2011 |isbn=978-1-61779-260-1 |issn=1064-3745 |doi=10.1007/978-1-61779-261-8_1 |pages=1–9}}</ref><ref name="Engelkamp Hatzakis Hofkens De Schryver 2006">{{cite journal |last=Engelkamp |first=Hans |last2=Hatzakis |first2=Nikos S. |last3=Hofkens |first3=Johan |last4=De Schryver |first4=Frans C. |last5=Nolte |first5=Roeland J. M. |last6=Rowan |first6=Alan E. |title=Do enzymes sleep and work? |journal=Chemical Communications |publisher=Royal Society of Chemistry (RSC) |issue=9 |year=2006 |issn=1359-7345 |doi=10.1039/b516013h |page=935}}</ref><ref name="Bard 2008" /><ref name="Walt pp. 1258–1263">{{cite journal |last=Walt |first=David R. |title=Optical Methods for Single Molecule Detection and Analysis |journal=Analytical Chemistry |publisher=American Chemical Society (ACS) |volume=85 |issue=3 |date=19 December 2012 |issn=0003-2700 |doi=10.1021/ac3027178 |pages=1258–1263}}</ref>
''' Boris Rotman''' (born 1924), aka '''Marcos Boris Rotman''', is an American [[immunologist]]― [[molecular biologist]] and professor [[emeritus]] of [[Medical Science]] at [[Alpert Medical School]] of [[Brown University]].<ref>{{cite web |title=Brown University |url=http://www.brown.edu/Faculty/Retirement/people/Emeriti.html|accessdate=10 October 2018}}</ref>
. He is widely recognized for performing the first [[single molecule experiment]]s in biology.<ref>{{Cite journal |last=Lord |first=S. J. |last2=Lee, H. D |first2=Moerner, W. E. |date=2010 |title=Single-Molecule Spectroscopy and Imaging of Biomolecules in Living Cells |url= |journal=Anal. Chem. |volume=82 |pages=2192–2203 |doi= |via=}}</ref><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" />


== Education ==
== Education ==
Boris Rotman attended elementary and high school at the [[Instituto Nacional]] of Chile. In 1942, he won a scholarship to attend the [[Universidad Técnica Federico Santa Maria]], he graduated with a chemical engineering degree in 1948. In 1950, he entered the [[University of Illinois]] and in 1952
Rotman attended elementary and high school at the [[Instituto Nacional]] of Chile. In 1942, he won a scholarship to attend the [[Universidad Técnica Federico Santa Maria]], from where he graduated with a chemical engineering degree in 1948. In 1950, he entered the [[University of Illinois]] and in 1952 earned a PhD in [[biochemistry]]/[[microbiology]]. His mentors at University of Illinois were [[Salvador E. Luria]] ([[Nobel laureate]] 1969) and [[Sol Spiegelman]] ([[Albert Lasker Award for Basic Medical Research]], 1974). After graduation, Rotman was a postdoctoral researcher in the group of [[Joshua Lederberg]] (Nobel laureate 1958) at [[University of Wisconsin-Madison]], and later, in the laboratory of [[Bernard D. Davis]] at [[Harvard Medical School]].<ref name="SOVA">{{cite web |title=The History of the Cell Sorter Interviews · SOVA |website=SOVA |url=https://sova.si.edu/record/SIA.FARU9554 |access-date=22 June 2019}}</ref>
earned a PhD in [[Biochemistry]]/[[Microbiology]]. His mentors at U. of Illinois were [[Salvador E. Luria]] ([[Nobel laureate]] 1969) and [[Sol Spiegelman]] ([[Albert Lasker Award for Basic Medical Research]], 1974). After graduation, Rotman was postdoctoral researcher in the group of [[Joshua Lederberg]] (Nobel laureate 1958) at [[University of Wisconsin-Madison]], and later, in the laboratory of [[Bernard D. Davis]] at [[Harvard Medical School]].


== Research career ==
== Research career ==
In 1961, Rotman developed a system capable of measuring the enzymatic activity of individual molecules of beta galactosidase and used it to conduct the first [[single-molecule experiment]] in biology.<ref name=":0">Rotman, B. (1961) Measurement of activity of single molecules of β-D-galactosidase. Proc Natl Acad Sci USA 47, 1981-1991.(doi:10.1073/pnas.47.12.1981.doi:10.1073/pnas.47.12.1981</ref><ref name=":1">Knight, Alex E. (2011) Single Enzyme Studies: A Historical Perspective Methods Mol Biol. 778:1-9.</ref><ref name=":2">Engelkamp, Hans, Hatzakis, Nikos S., Hofkens, Johan, De Schryver, Frans C., Roeland J. M. Nolte, and Alan E. Rowan. (2006) Do enzymes sleep and work? Chem. Commun., 935–940.</ref><ref name=":3">Bard, Allen J. (2008)</ref><ref name=":4">David R. Walt (2013) Optical methods for single molecule detection and analysis. Anal Chem. 85: 1258–1263</ref>
In 1961, Rotman developed a system capable of measuring the enzymatic activity of individual molecules of beta-galactosidase and used it to conduct the first [[single-molecule experiment]] in biology.<ref name="Rotman pp. 1981–1991">{{cite journal |last=Rotman |first=B. |title=Measurement of activity of single molecules of β-D-galactosidase |journal=Proceedings of the National Academy of Sciences |publisher=Proceedings of the National Academy of Sciences |volume=47 |issue=12 |date=1 December 1961 |issn=0027-8424 |doi=10.1073/pnas.47.12.1981 |pages=1981–1991}}</ref><ref name="Knight 2011 pp. 1–9" /><ref name="Engelkamp Hatzakis Hofkens De Schryver 2006" /><ref name="Bard 2008">Bard, Allen J. (2008)</ref><ref name="Walt pp. 1258–1263" />


These early experiments remained obscure for more than 30 years, but they are now recognized as pioneering and highly influential.<ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" /> A review states, "Indeed, this paper is the origin not only of the field of single-molecule enzymology, but also of much subsequent single-molecule research."<ref name=":1" /> The significance of [[single-molecule experiment]]s derives from their capacity to provide fundamental insights that are not attainable by conventional experimentation. For example: (a) Enzyme turnover can be measured directly from the number of fluorescent molecules of product produced by an individual enzyme molecule. (b) Studying heat inactivation of an enzyme at the single molecule level uncovered unprecedented mechanisms. Namely, heating causes an all-or-none distribution of enzymatic activity, i. e., the molecular population consists of either fully active or completely inactive enzyme molecules.<ref name=":0" /> This experiment rules out an alternative plausible mechanism postulating that partial heat inactivation produces enzyme molecules with partial activity; (c) In contrast, partial inactivation of beta-galactosidase resulting from storing crystalline enzyme under ammonium sulfate at low temperature (3-6&nbsp;°C) for several years, causes a uniform distribution of partially inactivated enzyme molecules,<ref>{{Cite book |title=The Lactose Operon |publisher= |year=1970 |isbn=978-0-317-11809-4 |location= |pages=}}</ref> (d) A [[point mutation]] in the [[lacZ]] gene alters [[beta-galactosidase]] activity producing a uniform populations of beta-galactosidase molecules with individual partial activity.<ref name=":0" />
These early experiments remained obscure for more than 30 years, but they are now recognized as pioneering and highly influential.<ref name="Knight 2011 pp. 1–9" /><ref name="Engelkamp Hatzakis Hofkens De Schryver 2006" /><ref name="Bard 2008" /><ref name="Walt pp. 1258–1263" /> A review states, "Indeed, this paper is the origin not only of the field of single-molecule enzymology, but also of much subsequent single-molecule research."<ref name="Knight 2011 pp. 1–9" /> The significance of [[single-molecule experiment]]s derives from their capacity to provide fundamental insights that are not attainable by conventional experimentation. For example (a) Enzyme turnover can be measured directly from the number of fluorescent molecules of product produced by an individual enzyme molecule. (b) Studying heat inactivation of an enzyme at the single molecule level uncovered unprecedented mechanisms. Namely, heating causes an all-or-none distribution of enzymatic activity, i. e., the molecular population consists of either fully active or completely inactive enzyme molecules.<ref name="Rotman pp. 1981–1991" /> This experiment rules out an alternative plausible mechanism postulating that partial heat inactivation produces enzyme molecules with partial activity; (c) In contrast, partial inactivation of beta-galactosidase resulting from storing crystalline enzyme under ammonium sulfate at low temperature (3-6&nbsp;°C) for several years, causes a uniform distribution of partially inactivated enzyme molecules,<ref>{{Cite book |title=The Lactose Operon |publisher= |year=1970 |isbn=978-0-317-11809-4 |location= |pages=}}</ref> (d) A [[point mutation]] in the [[lacZ]] gene alters [[beta-galactosidase]] activity producing a uniform populations of beta-galactosidase molecules with individual partial activity.<ref name="Rotman pp. 1981–1991" />


It is noteworthy that the first single-molecule experiment utilized two innovative technologies, [[Droplet-based microfluidics|droplet-based]] [[Microfluidics in chemical biology|microfluidics]] and fluorogenic substrates. The former was developed by J. F. Collins to measure penicillinase content of individual ''Bacillus'' ''lichenformis'',<ref>{{Cite journal |last=Collins |first=J. F. |date=1962 |title=Estimation of penicillinase in single bacterial cells |url= |journal=Biochem. J. |volume=82 |pages=28 P |via=}}</ref>. The latter, fluorogenic substrates are non-fluorescent compounds yielding fluorescent products upon enzymatic action. Fluorogenic substrates serve to increase sensitivity of enzyme assays and many are commercially available.
It is noteworthy that the first single-molecule experiment utilized two innovative technologies, [[Droplet-based microfluidics|droplet-based]] [[Microfluidics in chemical biology|microfluidics]] and fluorogenic substrates. The former was developed by J. F. Collins to measure penicillinase content of individual ''[[Bacillus licheniformis]]''.<ref>{{Cite journal |last=Collins |first=J. F. |date=1962 |title=Estimation of penicillinase in single bacterial cells |url= |journal=Biochem. J. |volume=82 |pages=28 P |via=}}</ref> The latter, fluorogenic substrates are non-fluorescent compounds yielding fluorescent products upon enzymatic action. Fluorogenic substrates serve to increase the sensitivity of enzyme assays and many are commercially available.


In 1966, Rotman and Papermaster discovered [[fluorochromasia]], a universal cellular phenomenon characterized by immediate appearance of bright green fluorescence inside viable cells upon exposure to certain membrane permeable fluorogenic substrates such as [[Fluorescein diacetate hydrolysis|fluorescein diacetate]], fluorescein dibutyrate and fluorescein dipropionate. The phenomenon is commonly used to measure cellular viability of many different species including animals, embryos, plants, and microorganisms.
In 1966, Rotman and Papermaster discovered [[fluorochromasia]], a universal cellular phenomenon characterized by the immediate appearance of bright green fluorescence inside viable cells upon exposure to certain membrane permeable fluorogenic substrates such as [[Fluorescein diacetate hydrolysis|fluorescein diacetate]], fluorescein dibutyrate, and fluorescein dipropionate.<ref name="Pilet 2012 p. 29">{{cite book |last=Pilet |first=P.E. |title=The Physiological Properties of Plant Protoplasts |publisher=Springer Berlin Heidelberg |series=Proceedings in Life Sciences |year=2012 |isbn=978-3-642-70144-3 |url=https://books.google.com/books?id=SfD0CAAAQBAJ&pg=PA29 |access-date=22 June 2019 |page=29 |quote=The other fluorochrome, fluorescein diacetate, first shown in 1966 (Rotman and Papermaster 1966) to induce fluorescence in animal cells was subsequently adapted to plant cells (Heslop-Harrison and Heslop-Harrison 1970, Widholm 1972) ...}}</ref> The phenomenon is commonly used to measure cellular viability of many different species including animals, embryos, plants, and microorganisms.


In 1968, Rotman and Celada reported existence of a subset of [[antibodies]] with the unprecedented ability to restore the activity of mutated molecules of defective beta-galactosidase by [[conformational change]].<ref>{{Cite journal |last=Rotman |first=M.B. |last2=Celada |first2=F. |date=1968 |title=Antibody-mediated activation of a defective beta-D-galactosidase extracted from an Escherichia coli mutant |url= |journal=Proc Natl Acad Sci U S A |volume=60 |pages=660–667 |via=}}</ref> Subsequently, this exceptional ability of some antibodies has been subject of many studies.<ref>{{Cite book |title=Protein Conformation as an Immunological Signal |last=Celada |first=Franco |last2=Schumaker, Verne |last3=Sercarz, Eli E |publisher=Plenum Press, New York |year=1983 |isbn= |location= |pages=}}</ref>
In 1968, Rotman and Celada reported existence of a subset of [[antibodies]] with the unprecedented ability to restore the activity of mutated molecules of defective beta-galactosidase by [[conformational change]].<ref name="Rotman Celada pp. 660–667">{{cite journal |last=Rotman |first=M. B. |last2=Celada |first2=F. |title=Antibody-mediated activation of a defective beta-D-galactosidase extracted from an Escherichia coli mutant. |journal=Proceedings of the National Academy of Sciences |publisher=Proceedings of the National Academy of Sciences |volume=60 |issue=2 |date=1 June 1968 |issn=0027-8424 |doi=10.1073/pnas.60.2.660 |pages=660–667}}</ref> Subsequently, this exceptional ability of some antibodies has been subject of many studies.<ref name="Celada Schumaker Sercarz 2012">{{cite book |last=Celada |first=F. |last2=Schumaker |first2=V.N. |last3=Sercarz |first3=E.E. |title=Protein Conformation as an Immunological Signal |publisher=Springer US |year=2012 |isbn=978-1-4613-3778-2 |url=https://books.google.com/books?id=lpbbBwAAQBAJ |access-date=22 June 2019 |page=240}}</ref>


== Awards ==
== Awards ==
In 1999, Rotman received the State of [[Rhode Island]] Governor's award for Scientific Excellence.<ref>{{cite web |title=Brown University |url=https://vivo.brown.edu/display/mrotman |accessdate=12 August 2018}}</ref>
In 1999, Rotman received the State of [[Rhode Island]] Governor's Award for Scientific Excellence.<ref name="Researchers @ Brown 2019">{{cite web |title=Rotman, Boris |website=Researchers @ Brown |date=14 February 2019 |url=https://vivo.brown.edu/display/mrotman |archive-url=http://web.archive.org/web/20190214111713/https://vivo.brown.edu/display/mrotman |archive-date=14 February 2019 |dead-url=no |access-date=22 June 2019}}</ref>

== Selected publications ==
* {{cite journal |last=Rotman |first=B. |last2=Spiegelman |first2=S. |title=On the origin of the carbon in the induced synthesis β-galactosidase in Escherichia coli |journal=Journal of Bacteriology |volume=68 |issue=4 |date=1 October 1954 |issn=0021-9193 |pmid=13201546 |pages=419–429 |url=https://jb.asm.org/content/68/4/419 |access-date=22 June 2019}}
* {{cite journal |last=Rotman |first=B. |title=Measurement of activity of single molecules of β-D-galactosidase |journal=Proceedings of the National Academy of Sciences |publisher=Proceedings of the National Academy of Sciences |volume=47 |issue=12 |date=1 December 1961 |issn=0027-8424 |doi=10.1073/pnas.47.12.1981 |pages=1981–1991}}
* {{cite journal |url=https://www.jstor.org/stable/71664 |title=Fluorogenic Substrates for &#x3b2; -D-galactosidases and Phosphatases Derived from Fluorescein (3, 6-dihydroxyfluoran) and Its Monomethyl Ether |date=22 June 1963 |publisher= |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=50 |issue=1 |pages=1–6 |accessdate=22 June 2019 |via=JSTOR}}
* {{cite journal |last=Rotman |first=B. |last2=Papermaster |first2=B. W. |title=Membrane properties of living mammalian cells as studied by enzymatic hydrolysis of fluorogenic esters. |journal=Proceedings of the National Academy of Sciences |publisher=Proceedings of the National Academy of Sciences |volume=55 |issue=1 |date=1 January 1966 |issn=0027-8424 |doi=10.1073/pnas.55.1.134 |pages=134–141}}
* {{cite journal | title=Transport systems for galactose and galactosides in Escherichia coli: I. Genetic determination and regulation of the methyl-galactoside permease | journal=Journal of Molecular Biology | volume=16 | issue=1 | date=1 March 1966 | issn=0022-2836 | doi=10.1016/S0022-2836(66)80261-9 | pages=42–50 | url=https://www.sciencedirect.com/science/article/pii/S0022283666802619 | access-date=22 June 2019}}
* {{cite journal | title=A fluorochromatic test for immunocytotoxicity against tumor cells and leucocytes in agarose plates | journal=Proceedings of the National Academy of Sciences | volume=57 | issue=3 | date=1 March 1967 | issn=0027-8424 | pmid=16591510 | doi=10.1073/pnas.57.3.630 | url=https://www.pnas.org/content/57/3/630 | access-date=22 June 2019 | page=}}
* {{cite journal |last=Rotman |first=M B |last2=Celada |first2=F |title=Antibody-mediated activation of a defective beta-D-galactosidase extracted from an Escherichia coli mutant |journal=Proceedings of the National Academy of Sciences |volume=60 |issue=2 |date=1 June 1968 |issn=0027-8424 |pmid=4882747 |doi=10.1073/pnas.60.2.660 |pages=660–667 |url=https://www.pnas.org/content/60/2/660 |access-date=22 June 2019}}
* {{cite journal |title=Transport systems for galactose and galactosides in Escherichia coli: II. Substrate and inducer specificities |journal=Journal of Molecular Biology |volume=36 |issue=2 |date=14 September 1968 |issn=0022-2836 |doi=10.1016/0022-2836(68)90379-3 |pages=247–260 |url=https://www.sciencedirect.com/science/article/pii/0022283668903793 |access-date=22 June 2019}}
* {{cite journal |title=Distribution of suboptimally induced β-d-galactosidase in Escherichia coli: The enzyme content of individual cells |journal=Journal of Molecular Biology |volume=73 |issue=1 |date=1 January 1973 |issn=0022-2836 |doi=10.1016/0022-2836(73)90160-5 |pages=77–91 |url=https://www.sciencedirect.com/science/article/pii/0022283673901605 |access-date=22 June 2019}}


== References ==
== References ==

Revision as of 09:31, 22 June 2019

Marcos Boris Rotman
Boris Rotman, 2011
Born1924 (age 99–100)
Buenos Aires, Argentina
CitizenshipUSA
Alma materUniversity of Illinois (PhD, 1952)
Universidad Tecnica Federico Santa Maria (M.S., 1948)
Known forFirst single molecule experiment in biology
SpouseRosario Guzman-Rotman (married 1993)
ChildrenJessica R. Yates
AwardsState of Rhode Island Governor's Award for Scientific Achievement (1990)
Scientific career
FieldsBiochemistry
Molecular biology
InstitutionsBrown University
Stanford Medical School
Syntex Institute for Molecular Biology, Stanford
Escuela de Medicina, Universidad de Chile
Karolinska Institute
Weizmann Institute of Science – Dept. of Chemical Immunology
Thesis A heritable conversion of phenotype in yeast.  (1952)
Doctoral advisorSalvador Luria and Sol Spiegelman
Other academic advisorsJoshua Lederberg

Marcos Boris Rotman (born 1924), is an American immunologist–molecular biologist and professor emeritus of Medical Science at Alpert Medical School of Brown University.[1] He is widely recognized for performing the first single molecule experiments in biology.[2][3][4][5][6]

Education

Rotman attended elementary and high school at the Instituto Nacional of Chile. In 1942, he won a scholarship to attend the Universidad Técnica Federico Santa Maria, from where he graduated with a chemical engineering degree in 1948. In 1950, he entered the University of Illinois and in 1952 earned a PhD in biochemistry/microbiology. His mentors at University of Illinois were Salvador E. Luria (Nobel laureate 1969) and Sol Spiegelman (Albert Lasker Award for Basic Medical Research, 1974). After graduation, Rotman was a postdoctoral researcher in the group of Joshua Lederberg (Nobel laureate 1958) at University of Wisconsin-Madison, and later, in the laboratory of Bernard D. Davis at Harvard Medical School.[7]

Research career

In 1961, Rotman developed a system capable of measuring the enzymatic activity of individual molecules of beta-galactosidase and used it to conduct the first single-molecule experiment in biology.[8][3][4][5][6]

These early experiments remained obscure for more than 30 years, but they are now recognized as pioneering and highly influential.[3][4][5][6] A review states, "Indeed, this paper is the origin not only of the field of single-molecule enzymology, but also of much subsequent single-molecule research."[3] The significance of single-molecule experiments derives from their capacity to provide fundamental insights that are not attainable by conventional experimentation. For example (a) Enzyme turnover can be measured directly from the number of fluorescent molecules of product produced by an individual enzyme molecule. (b) Studying heat inactivation of an enzyme at the single molecule level uncovered unprecedented mechanisms. Namely, heating causes an all-or-none distribution of enzymatic activity, i. e., the molecular population consists of either fully active or completely inactive enzyme molecules.[8] This experiment rules out an alternative plausible mechanism postulating that partial heat inactivation produces enzyme molecules with partial activity; (c) In contrast, partial inactivation of beta-galactosidase resulting from storing crystalline enzyme under ammonium sulfate at low temperature (3-6 °C) for several years, causes a uniform distribution of partially inactivated enzyme molecules,[9] (d) A point mutation in the lacZ gene alters beta-galactosidase activity producing a uniform populations of beta-galactosidase molecules with individual partial activity.[8]

It is noteworthy that the first single-molecule experiment utilized two innovative technologies, droplet-based microfluidics and fluorogenic substrates. The former was developed by J. F. Collins to measure penicillinase content of individual Bacillus licheniformis.[10] The latter, fluorogenic substrates are non-fluorescent compounds yielding fluorescent products upon enzymatic action. Fluorogenic substrates serve to increase the sensitivity of enzyme assays and many are commercially available.

In 1966, Rotman and Papermaster discovered fluorochromasia, a universal cellular phenomenon characterized by the immediate appearance of bright green fluorescence inside viable cells upon exposure to certain membrane permeable fluorogenic substrates such as fluorescein diacetate, fluorescein dibutyrate, and fluorescein dipropionate.[11] The phenomenon is commonly used to measure cellular viability of many different species including animals, embryos, plants, and microorganisms.

In 1968, Rotman and Celada reported existence of a subset of antibodies with the unprecedented ability to restore the activity of mutated molecules of defective beta-galactosidase by conformational change.[12] Subsequently, this exceptional ability of some antibodies has been subject of many studies.[13]

Awards

In 1999, Rotman received the State of Rhode Island Governor's Award for Scientific Excellence.[14]

Selected publications

References

  1. ^ "Brown University". Retrieved 10 October 2018.
  2. ^ Lord, Samuel J.; Lee, Hsiao-lu D.; Moerner, W. E. (15 March 2010). "Single-Molecule Spectroscopy and Imaging of Biomolecules in Living Cells". Analytical Chemistry. 82 (6). American Chemical Society (ACS): 2192–2203. doi:10.1021/ac9024889. ISSN 0003-2700.
  3. ^ a b c d Knight, Alex E. (2011). "Single Enzyme Studies: A Historical Perspective". Single Molecule Enzymology. Totowa, NJ: Humana Press. pp. 1–9. doi:10.1007/978-1-61779-261-8_1. ISBN 978-1-61779-260-1. ISSN 1064-3745.
  4. ^ a b c Engelkamp, Hans; Hatzakis, Nikos S.; Hofkens, Johan; De Schryver, Frans C.; Nolte, Roeland J. M.; Rowan, Alan E. (2006). "Do enzymes sleep and work?". Chemical Communications (9). Royal Society of Chemistry (RSC): 935. doi:10.1039/b516013h. ISSN 1359-7345.
  5. ^ a b c Bard, Allen J. (2008)
  6. ^ a b c Walt, David R. (19 December 2012). "Optical Methods for Single Molecule Detection and Analysis". Analytical Chemistry. 85 (3). American Chemical Society (ACS): 1258–1263. doi:10.1021/ac3027178. ISSN 0003-2700.
  7. ^ "The History of the Cell Sorter Interviews · SOVA". SOVA. Retrieved 22 June 2019.
  8. ^ a b c Rotman, B. (1 December 1961). "Measurement of activity of single molecules of β-D-galactosidase". Proceedings of the National Academy of Sciences. 47 (12). Proceedings of the National Academy of Sciences: 1981–1991. doi:10.1073/pnas.47.12.1981. ISSN 0027-8424.
  9. ^ The Lactose Operon. 1970. ISBN 978-0-317-11809-4.
  10. ^ Collins, J. F. (1962). "Estimation of penicillinase in single bacterial cells". Biochem. J. 82: 28 P.
  11. ^ Pilet, P.E. (2012). The Physiological Properties of Plant Protoplasts. Proceedings in Life Sciences. Springer Berlin Heidelberg. p. 29. ISBN 978-3-642-70144-3. Retrieved 22 June 2019. The other fluorochrome, fluorescein diacetate, first shown in 1966 (Rotman and Papermaster 1966) to induce fluorescence in animal cells was subsequently adapted to plant cells (Heslop-Harrison and Heslop-Harrison 1970, Widholm 1972) ...
  12. ^ Rotman, M. B.; Celada, F. (1 June 1968). "Antibody-mediated activation of a defective beta-D-galactosidase extracted from an Escherichia coli mutant". Proceedings of the National Academy of Sciences. 60 (2). Proceedings of the National Academy of Sciences: 660–667. doi:10.1073/pnas.60.2.660. ISSN 0027-8424.
  13. ^ Celada, F.; Schumaker, V.N.; Sercarz, E.E. (2012). Protein Conformation as an Immunological Signal. Springer US. p. 240. ISBN 978-1-4613-3778-2. Retrieved 22 June 2019.
  14. ^ "Rotman, Boris". Researchers @ Brown. 14 February 2019. Archived from the original on 14 February 2019. Retrieved 22 June 2019. {{cite web}}: Unknown parameter |dead-url= ignored (|url-status= suggested) (help)
Retrieved from "https://en.wikipedia.org/w/index.php?title=Boris_Rotman&oldid=902927182"