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Structure and Function of Centrosomal Self-Assemblies by X-ray crystallography, NMR, or Cryo-EM

National Cancer Institute, Bethesda, MD and surrounding area

Position Description:

The architecture of a cell is established through varying degrees of hierarchical organizations from single molecules to macromolecular assemblies.  Investigating how these molecules interact with one another to form a higher-order structural entity with a new biological function is a key step to unlocking the mystery of life.  We are mainly interested in understanding the molecular bases of how the physicochemical properties of pericentriolar scaffold proteins drive the formation of micron-scale self-assemblies with distinct cellular functions.  Recently, we found that human polo-like kinase 4, a key regulator of centriole duplication, forms a high M.W. complex with centrosomal scaffold proteins, which cooperatively self-assemble into a higher-order architecture around a centriole in a concentration-dependent manner. Notably, a failure in these events can result in abnormal centrosome numbers, improper spindle formation, and chromosome missegregation that ultimately lead to the development of various human diseases, including cancer, ciliopathy, and microcephaly.  Thus, we aim to elucidate the molecular mechanism underlying the assembly of pericentriolar architectures to ultimately understand the etiology of centrosome-associated human diseases.

Fellows, who have an expertise in X-ray crystallography, NMR, and/or Cryo-EM with a keen interest in investigating the structure and function of centrosomal scaffold proteins are encouraged to apply.

Selected publications:
  1. Phase separation of Polo-like kinase 4 by autoactivation and clustering drives centriole biogenesis. Park JE, Zhang L, Bang JK, Andresson T, DiMaio F, Lee KS. Nat Commun. 4959, 2019. 
  2. Molecular architecture of a cylindrical self-assembly at human centrosomes. Kim TS, Zhang L, Ahn JI, Meng L, Chen Y, Lee E, Bang JK, Lim JM, Ghirlando R, Fan L, Wang YX, Kim BY, Park JE, Lee KS. Nat Commun. 10(1): 1151, 2019. 
  3. Wei, Z., et al., 2020. Requirement of the Cep57-Cep63 interaction for proper Cep152 recruitment and centriole duplication. Mol. Cell. Biol. 40:e00535. Featured article (Cover art)
  4. Ahn, J. I., et al., 2020. Phase separation and versatile capacity of pericentriolar scaffold proteins drive the formation of higher-order self-assemblies at human centrosomes. Cell Cycle. Nov 18:1-21.
  5. Lee, K. S., et al., 2020. A self-assembled cylindrical platform for Plk4-induced centriole biogenesis. Open Biol. 10:200102 (Invited review). Featured article (Cover art)

Qualifications:

Applicants should have a Ph.D. (or expected) or M.D. equivalent at the time of joining the lab. For more information, please click the link below. https://ccr.cancer.gov/Laboratory-of-Metabolism/kyung-s-lee

To Apply:

Please send CV and three names of references to Dr. Kyung Lee (kyunglee@mail.nih.gov).

 

This post will be available until July 27, 2021 or until filled.

This position is subject to a background investigation.

The NIH is dedicated to building a diverse community in its training programs.