Tony’s biosketch

NAME: Anthony A Hyman

POSITION TITLE: Institute Director

EDUCATION/TRAINING

1. Personal Statement.

Prof. Dr. Anthony Hyman is Director and Group Leader at the Max Planck Institute of Molecular Cell Biology and Genetics. 1984 he received his BSc first class in Zoology from the University College in London, where he had also been working as research Assistant in 1981.  From 1985 to 1987 he wrote his PhD about “The establishment of division axes in early C.elegans embryos” under the supervision of Dr. John White at the Laboratory of Molecular Biology, MRC in Cambridge, England. After that he moved to San Francisco where he did his postdoctoral research in the lab of Prof. Tim Mitchison at the University of California investigating the mechanism of chromosome movement studied in vitro. 1993 he became Group Leader at the European Molecular Biology Laboratory in Heidelberg, before he moved to Dresden in 1999 as a founding director of the Max Planck Institute for Molecular Cell Biology and Genetics. This notable addition to the European scientific scene is already well known for its positive working environment for young scientists. He is best known for his work on the role of phase separation in formation of biological compartments.

1. Positions and Honors

Positions and Employment

1993 – 1997                Group Leader: EMBL, Heidelberg

1997 – present                       Director, MPI-CBG Dresden

Selected professional service

2014 – 2017                Council Member, American Society of Cell Biology (ASCB)

2015 – present                       SAB, Allen Institute for Cell Science, Seattle, Washington, USA

2017 – present                 Chair, Welcome Trust Strategy committee.

Selected Honors

2003    EMBO Gold Medal

2007    Elected fellow of the Royal Society

2011    Gottfried Wilhelm Leibniz Prize

2017    Schleiden Medal, German Academy of Science.

1. Contributions to Science

Hyman began his career as a PhD student at the LMB in Cambridge, in Sydney Brenner’s C.elegans group, under the supervision of John White. There he published a paper on orientation of the cell division axes during the early cell divisions of C.elegans embryos using microscopy and microsurgery that is still cited today (1).

• Hyman, A.A. and White, J.G. (1988) Determination of cell division axes in the early embryogenesis of Caenorhabditis elegans.  Cell Biol. 105:2123-2135

Hyman next pursued post-doctoral research on kinetochores in the laboratory of Tim Mitchison at the University of San Francisco CA (2).  There, he characterized a number of important tools for studying microtubule dynamics that are still in constant use (3), After starting his first independent group at the EMBL, he worked on the structural basis of microtubule dynamics, and how these dynamics are regulated by protein factors. (4,5,6).

• Hyman , A.A. and Mitchison, T.J. (1991). Two different microtubule-based motor activities with opposite polarities in kinetochores.  Nature 351:206-211
• Hyman, A.A., Salser , Drechsel, D., Unwin N., and Mitchison T.J.. (1992)  The role of GTP hydrolysis in microtubule dynamics: Information from a slowly-hydrolyzeable analogue, GMPCPP.  Mol. Biol of Cell. 3: 1155-116
• Hyman, A.A Chretian, C. Arnal, I and Wade R. (1995). Structural changes accompanying GTP hydrolysis in microtubules: information from a slowly hydrolyzable analogue GMPCPP.  Cell Biol. 128:  117-125
• Mueller T. Chretien D, Severin F. and Hyman A.A.  (1998. Structural changes at microtubule ends accompanying GTP hydrolysis: information from a slowly hydrolyzeable analogue of GTP, GMPCPP.   PNAS 95: 3661-3666
• Kinoshita, K, Isabelle Arnal, Arshad Desai, David N. Drechsel, and Anthony A. Hyman (2001). Reconstitution of Physiological Microtubule Dynamics Using Purified Components. Science 294: 1340-1343

While at EMBL, he worked closely with Dr Eric Karsenti:  Their shared work had a major influence on our current understanding of how a meiotic spindle can self-assemble, and by extension, illuminated principles for self organization of the cytoplasm more generally. Hyman, Karsenti, Heald and co-workers showed that in egg meiotic spindles, nucleation occurs around chromosomes, and then the spindle self-organized using motor proteins as well as local modulation of microtubule dynamics (7). Soon after starting at EMBL, Hyman initiated a program in C elegans embryology. He established two main lines of research in this area. One was a direct continuation of the ideas from his PhD, using increasingly sophisticated laser microsurgery to create abnormal distribution of forces in the cytoplasm, and inferring the distribution of forces from the ensuing behavior (8). He published two important papers using these methods. In a 2003 Science paper Grill and Hyman described the forces acting on microtubules at the cortex in detail. This elegant study borrowed ideas from classic work on ion channels that had not before been used to study the cytoskeleton (8,9). In a 2005 Nature paper, Bringmann and Hyman showed that both asters and spindle midzones send parallel signals to the cortex to induce cleavage furrows (10). This paper resolves a long-standing controversy in cytokinesis mechanism, and should allow molecular dissection of two parallel pathways in cytokinesis.

• Heald,   Tournebize, R.  Blank, T.  Sandaltzopoulos, R.  Becker, P.  Hyman, A and Karsenti, E.  (1996).  Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts.  Nature 382: 420-425
• Grill, S. Gonczy P.  Stelzer, E and Hyman A.A. (2001) Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo. Nature 409: 630-633
• Grill SW, Howard J, Schaffer E, Stelzer EH, Hyman AA. (2003). The distribution of active force generators controls mitotic spindle position. Science. 301: 518-521.
• Bringmann H and Hyman AA (2005). A cytokinesis furrow is positioned by two consecutive signals. Nature 436: 731-734

Hyman’s second line of research in the C elegans embryo used functional genomics to identify “parts lists” for different cytoplasmic processes, and then uses detailed microscopy and genetics to understand pathways underlying assembly of key mitotic organelles, such as centrosomes and kinetochores.  In two Nature papers (11,12), described the effect of knocking down every protein in the genome, using RNAi and video-microscopy.  His screen identified ~90% of the genes whose single loss of function creates defects in cell division (about 700), and for the first time defined the complexity of cell division in a multi-cellular organism. This screen lead to the discovery of the SAS proteins, which lead to the elucidation of a conserved pathway of centriole duplication (13). 

• Gonczy P, Echeverri G, Oegema K, Coulson A, Jones SJ, Copley RR, Duperon J, Oegema J, Brehm M, Cassin E, Hannak E, Kirkham M, Pichler S, Flohrs K, Goessen A, Leidel S, Alleaume AM, Martin C, Ozlu N, Bork P, Hyman AA. (2000). Functional genomic analysis of cell division in C.elegans using RNAi of genes on chromosome III. Nature 408: 331-336.
• Sonnichsen B et al, Hyman AA, Echeverri CJ. (2005). Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. 434:462-469
• Kirkham M, Mueller-Reichert T, Oegema K, Grill S, Hyman AA (2003). SAS-4 Is a C. elegans Centriolar Protein that Controls Centrosome Size. Cell 112: 575-587

Hyman moved to Dresden to be a founding director of the Max Planck Institute for Cell Biology and Genetics.  There, he began to work closely with Frank Julicher and Stephan Grill on the role of physics in understanding the organization of cells.  Using a combination of biophysics and modeling, he worked extensively on the ways in which the cell polarizes its cortex in the first cell division of C.elegans (14).  By collaborating with a biophysisist Daniel Mueller, he used atomic force microscopy to make important contributions to understanding the problem of cell size (15).

• Goehring, NW; Trong, PK; Bois, JS; Chowdhury, D; Nicola, EM; Hyman, AA; Grill, SW. (2011). Polarization of PAR Proteins by Advective Triggering of a Pattern-Forming System. SCIENCE: 334 (6059): 1137-1141
• Stewart, MP; Helenius, J; Toyoda, Y; Ramanathan, SP; Muller, DJ; Hyman, AA. (2011). Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding. Nature: 469 (7329): 226-230.

In 2009 his laboratory made a major discovery with broad implications for understanding the organization of cellular biochemistry and neurodegenerative disease.  As a postdoctoral fellow in his lab, Cliff Brangwynne, showed that protein-RNA granulesm have surprising liquid-like properties and form by phase separation (16,17).  He then went on to show that other organelles, such as nucleoli, also follow similar physical principles (18).  In 2015 he showed that that liquid-like FUS drops will convert into solid-like aggregates that are reminiscent of those seen in disease (19). This suggested that one of the driving forces for the onset of neurodegenerative disease could be aberrant liquid-solid phase transitions.  More recently, he proposed a novel role for ATP as a hydrotrope in regulation of protein solubility, in addition to its role as an energy source and proposed that idea that a general drop in ATP levels as cells age could contribute to increased protein insolubility which is characteristic of age (20).

• Brangwynne, CP; Eckmann, CR; Courson, DS; Julicher F and Hyman, AA, (2009). Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation. Science 324(5935); 1729-1732.
• Hyman AA, Weber CA, Jülicher F. (2014). Liquid-liquid phase separation in biology. Annu Rev Cell Dev Biol: 30:39-58
• Brangwynne, CP; Mitchison, TJ; Hyman, AA (2011). Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes. Proceedings of the National Academy of Sciences of the United States of America: 108(11): 4334-4339
• Patel A, Lee HO, Maharana S, Jawerth L, Jahnel M, Saha S, Pozniakovski A, Poser I, Stoynow S, Myers E, Drechsel D, Grill S, Hyman AA, Alberti S, (2015). A liquid to solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell: 162(5):1066-77.
• Patel, A.  Milinovska L, Saha S. Wang, J. Alberti, S. Krishnan, Y. Hyman, AA (2017).   ATP as a biological hydrotrope.  Science May 19;356(6339):753-75