Marc Kirschner

Last updated
Marc Kirschner
Plos kirschner.jpg
Born
Marc Wallace Kirschner

(1945-02-28) February 28, 1945 (age 78)
NationalityAmerican
Alma mater University of California, Berkeley (PhD)
Northwestern University (BA)
Known for cell cycle, embryonic development, facilitated evolution
Scientific career
Fields Systems biology
Institutions Harvard Medical School
University of California, San Francisco
Princeton University
Thesis Conformational changes in aspartate transcarbamylase  (1971)
Doctoral advisor Howard Schachman
Other academic advisorsJohn Gerhart
John Gurdon [ citation needed ]
Doctoral students Tim Stearns
Tim Mitchison [1] [2]
Website kirschner.hms.harvard.edu

Marc Wallace Kirschner (born February 28, 1945) is an American cell biologist and biochemist and the founding chair of the Department of Systems Biology at Harvard Medical School. He is known for major discoveries in cell and developmental biology related to the dynamics and function of the cytoskeleton, the regulation of the cell cycle, and the process of signaling in embryos, as well as the evolution of the vertebrate body plan. [3] He is a leader in applying mathematical approaches to biology. [4] He is the John Franklin Enders University Professor at Harvard University. [5] In 2021 he was elected to the American Philosophical Society. [6]

Contents

Education and early life

Kirschner was born in Chicago, Illinois, on February 28, 1945. He graduated from Northwestern University with a B.A. in chemistry in 1966. He received a Graduate Research Fellowship from the National Science Foundation in 1966 and earned a doctorate in biochemistry from the University of California, Berkeley in 1971. [7]

Career and research

He held postdoctoral positions at UC Berkeley and at the University of Oxford in England. He became assistant professor at Princeton University in 1972. In 1978 he was made professor at the University of California, San Francisco. In 1993, he moved to Harvard Medical School, where he served as the chair of the new Department of Cell Biology for a decade. He became the founding chair of the HMS Department of Systems Biology in 2003. He was named the John Franklin Enders University Professor in 2009. [5] In 2018, he was succeeded as Chair of the Department of Systems Biology by Galit Lahav. [8]

Kirschner studies how cells divide, how they generate their shape, how they control their size, and how embryos develop. In his eclectic lab, developmental work on the frog coexists with biochemical work on mechanism of ubiquitination, cytoskeleton assembly or signal transduction.

At Princeton, his early work on microtubules established their unusual molecular assembly from tubulin proteins and identified the first microtubule-stabilizing protein tau, [9] later shown to be a major component of the neurofibrillary tangles in Alzheimer's disease. In studies at UC San Francisco of the frog embryo as a model system of cell development, Kirschner identified the first inducer of embryonic differentiation, fibroblast growth factor (FGF), [10] an early finding in the field of signal transduction.

Kirschner's lab is also known for uncovering basic mechanisms of the cell cycle in eukaryotic cells. Working in Xenopus (frog) egg extracts, Kirschner and Andrew Murray showed that cyclin synthesis drives the cell cycle [11] and, later, that ubiquitin regulates levels of cyclin by marking the cell-cycle molecule for destruction. [12] His lab discovered and purified many of the components involved in cell cycle progression, including anaphase promoting complex (APC), the complex that ubiquitinates cyclin B. [13]

A second noted [14] finding was his discovery, with Tim Mitchison, of the dynamic instability of microtubules, [15] [16] In mitosis, for example, microtubules form the spindle that separates the chromosomes. The first step in spindle formation is the nucleation of microtubules by microtubule-organizing centers, which then grow in all directions. Microtubules that attach to a chromosome are stabilized and are therefore retained to form part of the spindle. Because of dynamic instability, some individual microtubules that are not stabilized are at risk of collapse (or “catastrophe” as Kirschner named it), allowing re-use of the tubulin monomers. This recognition of self-organization in biological systems has been highly influential, and helped shape the view of the cytoplasm as a collection of dynamic molecular machines. [17]

Kirschner is also interested in the evolutionary origins of the vertebrate body plan. Together with John Gerhart, he was instrumental in developing the acorn worm Saccoglossus kowalevskii into a model system [18] that could be used to study the divergence between hemichordates and chordates, and the evolution of the chordate nervous system. [19] [20]

Kirschner is a pioneer in using mathematical approaches to learn about central biological questions. For example, a model of the Wnt pathway he developed in collaboration with the late Reinhart Heinrich showed that new properties and constraints emerge when the individual biochemical steps are combined into a complete pathway. [21] [22] A talk he gave on mathematics and the future of medicine at a retreat for Department Chairs at Harvard Medical School in 2003 inspired the Dean, Joseph B. Martin, to found a new Department, the Department of Systems Biology, with Kirschner as founding chair. [3] Since then, Kirschner's lab has attracted many students and post-docs from theoretical backgrounds who wish to make the transition into biology. His lab is now a leader in using mathematical tools to analyze signaling pathways, [23] cell size control, [24] and the selectivity of drugs. [25]

In two books co-authored with John Gerhart, Kirschner has described the cellular and developmental underpinnings of the evolution of organisms, and the concept of "evolvability". [26] In the most recent book, Kirschner and Gerhart proposed a new theory of "facilitated variation" that aims to answer the question: How can small, random genetic changes be converted into useful changes in complex body parts? [27]

Public service

Kirschner has been an advocate for federal biomedical research funding and served as first chair of the Joint Steering Committee for Public Policy, a coalition of scientific societies he helped create in 1993 to educate the U.S. Congress on biomedical research and lobby for public funding of it. [28] In 2014, Kirschner (together with Bruce Alberts, Shirley Tilghman and Harold Varmus) called for a number of changes to the system of US biomedical science, with the intention of reducing "hypercompetition" [29] This publication led to the formation of an organization, Rescuing Biomedical Research, that aims to collect community input and propose changes to the structure of academic science in the USA. [30]

Kirschner helped launch the monthly, peer-reviewed journal PLoS Biology in October 2003 as a member of the editorial board and senior author of a paper in the inaugural issue. The journal was the first publishing venture from the San Francisco-based Public Library of Science (PLoS), which had begun three years previously as a grassroots organization of scientists advocating free and unrestricted access to the scientific literature [31]

Books

Awards and associations

Related Research Articles

<span class="mw-page-title-main">Microtubule</span> Polymer of tubulin that forms part of the cytoskeleton

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

<span class="mw-page-title-main">Hemichordate</span> Phylum of marine deuterostome animals

Hemichordata is a phylum which consists of triploblastic, enterocoelomate, and bilaterally symmetrical marine deuterostome animals, generally considered the sister group of the echinoderms. They appear in the Lower or Middle Cambrian and include two main classes: Enteropneusta, and Pterobranchia. A third class, Planctosphaeroidea, is known only from the larva of a single species, Planctosphaera pelagica. The class Graptolithina, formerly considered extinct, is now placed within the pterobranchs, represented by a single living genus Rhabdopleura.

<span class="mw-page-title-main">Evolutionary developmental biology</span> Comparison of organism developmental processes

Evolutionary developmental biology is a field of biological research that compares the developmental processes of different organisms to infer how developmental processes evolved.

<span class="mw-page-title-main">Kinetochore</span> Protein complex that allows microtubules to attach to chromosomes during cell division

A kinetochore is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. The term kinetochore was first used in a footnote in a 1934 Cytology book by Lester W. Sharp and commonly accepted in 1936. Sharp's footnote reads: "The convenient term kinetochore has been suggested to the author by J. A. Moore", likely referring to John Alexander Moore who had joined Columbia University as a freshman in 1932.

<span class="mw-page-title-main">Pharyngeal slit</span> Repeated openings that appear along the pharynx of chordates

Pharyngeal slits are filter-feeding organs found among deuterostomes. Pharyngeal slits are repeated openings that appear along the pharynx caudal to the mouth. With this position, they allow for the movement of water in the mouth and out the pharyngeal slits. It is postulated that this is how pharyngeal slits first assisted in filter-feeding, and later, with the addition of gills along their walls, aided in respiration of aquatic chordates. These repeated segments are controlled by similar developmental mechanisms. Some hemichordate species can have as many as 200 gill slits. Pharyngeal clefts resembling gill slits are transiently present during the embryonic stages of tetrapod development. The presence of pharyngeal arches and clefts in the neck of the developing human embryo famously led Ernst Haeckel to postulate that "ontogeny recapitulates phylogeny"; this hypothesis, while false, contains elements of truth, as explored by Stephen Jay Gould in Ontogeny and Phylogeny. However, it is now accepted that it is the vertebrate pharyngeal pouches and not the neck slits that are homologous to the pharyngeal slits of invertebrate chordates. Pharyngeal arches, pouches, and clefts are, at some stage of life, found in all chordates. One theory of their origin is the fusion of nephridia which opened both on the outside and the gut, creating openings between the gut and the environment.

Timothy John Mitchison is a cell biologist and systems biologist and Hasib Sabbagh Professor of Systems Biology at Harvard Medical School in the United States. He is known for his discovery, with Marc Kirschner, of dynamic instability in microtubules, for studies of the mechanism of cell division, and for contributions to chemical biology.

<span class="mw-page-title-main">Bruce Alberts</span> American biochemist (born 1938)

Bruce Michael Alberts is an American biochemist and the Chancellor’s Leadership Chair in Biochemistry and Biophysics for Science and Education, emeritus at the University of California, San Francisco. He has done important work studying the protein complexes which enable chromosome replication when living cells divide. He is known as an original author of the "canonical, influential, and best-selling scientific textbook" Molecular Biology of the Cell, and as Editor-in-Chief of Science magazine.

<span class="mw-page-title-main">Facilitated variation</span>

The theory of facilitated variation demonstrates how seemingly complex biological systems can arise through a limited number of regulatory genetic changes, through the differential re-use of pre-existing developmental components. The theory was presented in 2005 by Marc W. Kirschner and John C. Gerhart.

<span class="mw-page-title-main">CDC20</span> Protein-coding gene in the species Homo sapiens

The cell division cycle protein 20 homolog is an essential regulator of cell division that is encoded by the CDC20 gene in humans. To the best of current knowledge its most important function is to activate the anaphase promoting complex (APC/C), a large 11-13 subunit complex that initiates chromatid separation and entrance into anaphase. The APC/CCdc20 protein complex has two main downstream targets. Firstly, it targets securin for destruction, enabling the eventual destruction of cohesin and thus sister chromatid separation. It also targets S and M-phase (S/M) cyclins for destruction, which inactivates S/M cyclin-dependent kinases (Cdks) and allows the cell to exit from mitosis. A closely related protein, Cdc20homologue-1 (Cdh1) plays a complementary role in the cell cycle.

<span class="mw-page-title-main">CDC27</span> Protein-coding gene in the species Homo sapiens

Cell division cycle protein 27 homolog is a protein that in humans is encoded by the CDC27 gene.

<span class="mw-page-title-main">Deuterostome</span> Superphylum of bilateral animals

Deuterostomes are bilaterian animals of the superphylum Deuterostomia, typically characterized by their anus forming before the mouth during embryonic development. The three major clades of extant deuterostomes include chordates, echinoderms and hemichordates.

Symmetry breaking in biology is the process by which uniformity is broken, or the number of points to view invariance are reduced, to generate a more structured and improbable state. Symmetry breaking is the event where symmetry along a particular axis is lost to establish a polarity. Polarity is a measure for a biological system to distinguish poles along an axis. This measure is important because it is the first step to building complexity. For example, during organismal development, one of the first steps for the embryo is to distinguish its dorsal-ventral axis. The symmetry-breaking event that occurs here will determine which end of this axis will be the ventral side, and which end will be the dorsal side. Once this distinction is made, then all the structures that are located along this axis can develop at the proper location. As an example, during human development, the embryo needs to establish where is ‘back’ and where is ‘front’ before complex structures, such as the spine and lungs, can develop in the right location. This relationship between symmetry breaking and complexity was articulated by P.W. Anderson. He speculated that increasing levels of broken symmetry in many-body systems correlates with increasing complexity and functional specialization. In a biological perspective, the more complex an organism is, the higher number of symmetry-breaking events can be found.

In evolutionary developmental biology, inversion refers to the hypothesis that during the course of animal evolution, the structures along the dorsoventral (DV) axis have taken on an orientation opposite that of the ancestral form.

<span class="mw-page-title-main">Anthony A. Hyman</span> British biologist

Anthony Arie Hyman is a British scientist and director at the Max Planck Institute of Molecular Cell Biology and Genetics.

<span class="mw-page-title-main">Ronald Vale</span> American biochemist

Ronald David Vale ForMemRS is an American biochemist and cell biologist. He is a professor at the Department of Cellular and Molecular Pharmacology, University of California, San Francisco. His research is focused on motor proteins, particularly kinesin and dynein. He was awarded the Canada Gairdner International Award for Biomedical Research in 2019, the Shaw Prize in Life Science and Medicine in 2017 together with Ian Gibbons, and the Albert Lasker Award for Basic Medical Research in 2012 alongside Michael Sheetz and James Spudich. He is a fellow of the American Academy of Arts and Sciences and a member of the National Academy of Sciences. He was the president of the American Society for Cell Biology in 2012. He has also been an investigator at the Howard Hughes Medical Institute since 1995. In 2019, Vale was named executive director of the Janelia Research Campus and a vice president of HHMI; his appointment began in early 2020.

<span class="mw-page-title-main">James Ferrell</span>

James Ellsworth Ferrell is an American systems biologist. He is a Professor of Chemical and Systems Biology and Biochemistry at Stanford University School of Medicine. He was Chair of the Dept. of Chemical and Systems Biology from its inception in 2006 until 2011.

<span class="mw-page-title-main">Don W. Cleveland</span>

Don W. Cleveland is an American cancer biologist and neurobiologist.

<span class="mw-page-title-main">Evo-devo gene toolkit</span>

The evo-devo gene toolkit is the small subset of genes in an organism's genome whose products control the organism's embryonic development. Toolkit genes are central to the synthesis of molecular genetics, palaeontology, evolution and developmental biology in the science of evolutionary developmental biology (evo-devo). Many of them are ancient and highly conserved among animal phyla.

In biology, constructive development refers to the hypothesis that organisms shape their own developmental trajectory by constantly responding to, and causing, changes in both their internal state and their external environment. Constructive development can be contrasted with programmed development, the hypothesis that organisms develop according to a genetic program or blueprint. The constructivist perspective is found in philosophy, most notably developmental systems theory, and in the biological and social sciences, including developmental psychobiology and key themes of the extended evolutionary synthesis. Constructive development may be important to evolution because it enables organisms to produce functional phenotypes in response to genetic or environmental perturbation, and thereby contributes to adaptation and diversification.

Kristen Kroll is an American developmental and stem cell biologist and Professor of Developmental Biology at Washington University School of Medicine. Her laboratory studies transcriptional and epigenetic regulation of brain development and its disruption to cause neurodevelopmental disorders.

References

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  32. AAAS member lists in PDF
  33. Archived award citation
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  35. Harvey Prize 2015