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Nicole King

Nicole King

Howard Hughes Investigator and Associate Professor of Genetics, Genomics and Development*
*And Affiliate, Division of Cell and Developmental Biology

Lab Homepage: http://kinglab.berkeley.edu/

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Research Interests

The origin of animals represents one of the pivotal transitions in life’s history, and one of its greatest unsolved mysteries. While the fossil record remains silent regarding the rise of multicellularity, the genetic and developmental foundations of animal origins may be deduced from shared elements among extant animals and their protozoan relatives, the choanoflagellates. To better understand the origin and evolution of animals, we are:

  1. reconstructing the minimal genomic complexity of the unicellular progenitors of animals
  2. elucidating the ancestral functions of genes required for animal development
  3. characterizing the molecular mechanisms underlying choanoflagellate cell/developmental biology and the interactions between choanoflagellates and bacteria

Current Projects

Cell biology and colony development in choanoflagellates: The mechanisms by which choanoflagellates form multicelled colonies, establish cell polarity, and reproduce may provide crucial insights into the transition to multicellularity, but little is known about their cell biology or natural history. We have recently discovered that there is an unexpected amount of cell differentiation during the life history of the choanoflagellate Salpingoeca rosetta, including the formation of at least two different multicellular colonial forms.  These colonies form through a process of incomplete cytokinesis (rather than cell aggregation) such that the mature colony is a clonal individual.  In addition, neighboring cells in colonies are linked through fine intercellular bridges that may permit direct sharing of small molecules.  Our next goals are to investigate the genetic determinants of cell differentiation and colony formation, through the use of RNA-Seq approaches and the development of genetic screens.

Interspecies interactions in choanoflagellates: Our studies of the choanoflagellate S. rosetta have revealed that its ability to form rosette-shaped colonies is regulated by a chemical signal synthesized by prey bacteria from the genus Algoriphagus. Given the close evolutionary relationship of choanoflagellates to animals and the experimental tractability of the S. rosetta-Algoriphagus interaction, this pairing holds great potential for revealing fundamental mechanisms linking inter-kingdom signaling to morphogenesis.  We have been collaborating with the Clardy lab at Harvard Medical School to isolate and identify the bacterially-produced signaling molecule.  In addition, we have developed genetic approaches in Algoriphagus to dissect the necessary biosynthetic pathway.  Moving forward, a major goal is to isolate the S. rosetta receptor that allows it to perceive and respond to the Algoriphagus signal.

Using comparative genomics to investigate the ancestral animal genome: A key question in the origin of animals concerns how and when the “toolkit” of animal genes was assembled. To test whether genes required for animal development evolved before the origin of animal multicellularity, we have sequenced the genomes of the choanoflagellate Monosiga brevicollis and S. rosetta (in collaboration with the JGI and Broad Institute) and are currently preparing to sequence the transcriptomes of 19 additional cultured choanoflagellates as part of the Moore Foundation/NCGR Marine Microbial Eukaryote Transcriptome project. Genes shared only by choanoflagellates and animals were likely present in their common ancestor and may shed light on the transition to multicellularity. This work has already provided evidence that choanoflagellates express members of diverse protein families (e.g. receptor tyrosine kinases, cadherins, and C-type lectins) required for animal cell signaling and adhesion.

Investigating the ancient functions of genes required for multicellular development: The finding of signaling and adhesion gene homologs (e.g. cadherins, receptor tyrosine kinases, and protooncogenes) in choanoflagellates raises questions about how these genes functioned in the unicellular common ancestor of choanoflagellates and animals, and what role they played in the origin of multicellularity. By focusing on the study of cadherins, we have identified a set of previously unidentified cadherin families that were present in the last common ancestor of animals and their last common ancestor with choanoflagellates (the “urchoanimal”).  In addition, we have found that the important regulatory interaction between the transcription factor Max and its binding partner Mad evolved before the origin of animals.  Inferences about gene function in diverse choanoflagellates provide an important reference point for studies of gene family evolution in animals.

Selected Publications

Fairclough, S., Chen, Z., Kramer, E., Zhen, Q., Young, S., Robertson, H., Begovic, E., Richter, D.J., Russ, C., Westbrook, M.J., Manning, G., Lang, B.F., Haas, B., Nusbaum, C., King, N. Premetazoan genome evolution and the regulation of cell differentiation in the choanoflagellate Salpingoeca rosetta. Genome Biology, 14(2):R15.

Margaret McFall-Ngai, Michael G. Hadfield, Thomas C. G. Bosch, Hannah V. Carey, Tomislav Domazet-Loso, Angela E. Douglas, Nicole Dubilier, Gerard Eberl, Tadashi Fukami, Scott F. Gilbert, Ute Hentschel, Nicole King, Staffan Kjelleberg, Andrew H. Knoll, Natacha Kremer, Sarkis K. Mazmanian, Jessica L. Metcalf, Kenneth Nealson, Naomi E. Pierce, John F. Rawls, Ann Reid, Edward G. Ruby, Mary Rumpho, Jon G. Sanders, Diethard Tautz, and Jennifer J. Wernegreen. (2013) Animals in a bacterial world, a new imperative for the life sciences. PNAS. 110(9):3229-36

Alegado RA*, Brown LW*, Cao S, Dermenjian RK, Zuzow R, Fairclough SR, Clardy J§ and King N§ (2012) Bacterial regulation of colony development in the closest living relatives of animals. eLife. 1: e00013. eLife

Alegado RA, Grabenstatter JD, Zuzow R, Morris A, Huang SY, Summons RE and King N (2013) Algoriphagus machipongonensis sp. nov. co-isolated with a colonial choanoflagellate. IJSEM. Jan;63(Pt 1):163-8

Nichols SA, Roberts BW, Richter DJ, Fairclough SR and King N (2012) Origin of metazoan cadherin diversity and the antiquity of the classical cadherin/β-catenin complex. PNAS. 109(32):13046-51.

Dayel MJ, Alegado RA‡, Fairclough SR‡, Levin TC, Nichols SA, McDonald K and King N (2011) Cell differentiation and morphogenesis in the colony-forming choanoflagellate Salpingoeca rosettaDevelopmental Biology. 357: 73-82.

Young S, Diolaiti D, Conacci-Sorrell M, Ruiz-Trillo I, Eisenman RN, and King N (2011) Premetazoan Ancestry of the Myc-Max Network. MBE. 28(10):2961-71

Alegado RA, Ferriera S, Nusbaum C, Young SK, Zeng C, Imamovic A, Fairclough SR, King N (2010) Complete Genome Sequence of Algoriphagus sp. PR1, Bacterial Prey of a Colony-forming Choanoflagellate. J Bact 193:1485-6.

King N (2010) Nature and nurture in the evolution of cell biology. MBOC. 21: 3801-3802.

Fairclough SR, Dayel MJ, and King N (2010) Multicellular development in a choanoflagellate. Current Biology.20: R875-R876.

Abedin M and King N (2010) Diverse evolutionary paths to cell adhesion. Trends in Cell Biology.20: 734-742.

Sebé-Pedrós A, Roger AJ, Lang FB, King N, Ruiz-Trillo I. (2010) Ancient origin of the integrin-mediated adhesion and signaling machinery. Proc Natl Acad Sci U S A. May 17. [Epub ahead of print]

Nichols SA, Dayel MJ, and King N (2009) Genomic, phylogenetic, and cell biological insights into metazoan origins in Animal Evolution: Genes, Genomes, Fossils and Trees (Ed. MJ Telford and DTJ Littlewood, Oxford University Press).

Andrew Grimson, Mansi Srivastava, Bryony Fahey, Ben J. Woodcroft, H. Rosaria Chiang, Nicole King, Bernard M. Degnan, Daniel S. Rokhsar & David P. Bartel (2008) Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature. doi:10.1038/nature07415

King N, Young SL, Abedin M, Carr M, and Leadbeater BSC (2008) The choanoflagellates: heterotrophic nanoflagellates and the sister group of the Metazoa in Emerging Model Organisms (Cold Spring Harbor Laboratory Press). v.1.

Robin B. Kodner, Roger E. Summons, Ann Pearson, Nicole King, and Andrew H. Knoll. (2008) Sterols in a unicellular relative of the metazoans. PNAS.105(29):9897-902. PNAS

Wanqing Li, Susan L. Young, Nicole King, and W. Todd Miller. (2008) Signaling properties of a non-metazoan Src kinase and the evolutionary history of Src negative regulation. JBC. 283(22):15491-501. JBC

Nicole King, M. Jody Westbrook*, Susan L. Young*, Alan Kuo, Monika Abedin, Jarrod Chapman, Stephen Fairclough, Uffe Hellsten, Yoh Isogai, Ivica Letunic, Michael Marr, David Pincus, Nicholas Putnam, Antonis Rokas, Kevin J. Wright, Richard Zuzow, William Dirks, Matthew Good, David Goodstein, Derek Lemons, Wanqing Li, Jessica Lyons, Andrea Morris, Scott Nichols, Daniel J. Richter, Asaf Salamov, JGI Sequencing, Peer Bork, Wendell A. Lim, Gerard Manning, W. Todd Miller, William McGinnis, Harris Shapiro, Robert Tjian, Igor V. Grigoriev, Daniel Rokhsar. (2008)The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature. 451: 783-788. Open access.

Monika Abedin and Nicole King. (2008) The premetazoan ancestry of cadherins. Science. 319(5865):946-948. Free access through this link.

Iñaki Ruiz-Trillo, Gertraud Burger, Peter W. H. Holland, Nicole King, B. Franz Lang, Andrew J. Roger and Michael W. Gray. (2007) The origins of multicellularity: a multi-taxon genome initiative. Trends in Genetics. 23(3):113-8.Pubmed

Nichols S.A., Dirks, W., Pearse, J.S., and King N. (2006) Early evolution of animal cell signaling and adhesion genes. PNAS. 103(33):12451-6. Pubmed

King, N. (2005) Choanoflagellates. Current Biology. 15(4):R113-4. Pubmed

King, N. (2004) The unicellular ancestry of animal development. Developmental Cell. 7: 313–325. Pubmed

Last Updated 2013-05-31