Our research focuses on centromeres. We want to understand 1) What are the structural determinants of centromere formation and maintenance? 2) How does centromere recruits major effector proteins (like chromosome passenger complex and PP2A) in mitosis? and 3) What is the molecular basis for the activation of central mitotic kinase, Aurora B?
MASTER – Project: NUCLEOSOME BIOLOGY
A master thesis project is available at The University of Oslo in Sekulic lab at NCMM (Norwegian Center for Molecular Medicine). The aim of the project is to understand chromatin organization at the centromeres at molecular level. Centromere is a part of the chromosome that serves as foundation for formation of kinetochore, protein structure that attaches duplicated chromosomes to opposite poles of the dividing cell. Student will gain hands-on experience in purification of DNA, histones and other centromeric proteins using state-of-the-art technologies. He/she will assemble nucleosomes and nucleosome arrays in vitro for further biophysical analysis. It is essential to understand how is DNA packed in our cells and how is chromatin conformation used as basis for specifying the centromere. Without functional centromere, chromosomes are lost or broken – hallmark of cancers. The project is expected to last for 6 – 12 months. If you are interested please contact Nikolina Sekulic (Nikolina.sekulic@ncmm.uio.no)
Literature:
1. Sekulic N, Black BE. Preparation of Recombinant Centromeric Nucleosomes and Formation of Complexes with Nonhistone Centromere Proteins. Met Enzymol. 2016;573:67-96. doi: 10.1016/bs.mie.2016.01.014.
2. Falk JS*, Guo JY*, Sekulic N*, Smoak EM*, Mani T, Logsdon G, Gupta K, Jansen LT, Van Duyne GV, Vinogradov SA, Lampson MA, and Black BE. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere. Science. 2015 May 8;348(6235):699-703
* - Denotes equal contributions - co-authorship
3. Sekulic N, Bassett EA, Rogers DJ, Black BE. The structure of (CENP-A-H4)2 reveals physical features that mark centromeres. Nature. 2010 Sep 16;467(7313):347-51
MASTER – Project: MOLECULAR BASIS OF GENOME STABILITY
A master thesis project is available at The University of Oslo in Sekulic lab at NCMM (Norwegian Center for Molecular Medicine). The aim of the project is to use biochemical and biophysical techniques to characterize molecular interactions at the centromere that are assuring equal segregation of chromosomes during cell division. Student will gain hands on experience in molecular cloning, bacterial expression and purification of proteins using state-of-the-art equipment. Final stages of the project include assembly of multi-protein complexes, protein crystallization and use of X-ray crystallography to obtain 3D structure of the complex. The knowledge gained in this project will shed the light on the major mechanisms that safeguards our genome during chromosome segregation and will help understand how is this safety mechanism broken in cancer. The project is expected to last for 6 – 12 months. If you are interested please contact Nikolina Sekulic (Nikolina.sekulic@ncmm.uio.no)
The left cell is dividing properly, but the right one shows a chromosome segregation defect. The chromosomes are blue and the microtubules are red Copyright: Dartmouth Medicine.
Literature:
Watanabe, Y. Shugoshin: guardian spirit at the centromere. Curr. Opin. Cell Biol. 17, 590–595 (2005).
MASTER – Project: COMPUTATIONAL PROTEIN MODELING
A master thesis project is available at The University of Oslo. The project is a collaboration between the Sekulic lab at NCMM (Norwegian Center for Molecular Medicine) and the Cascella group at The Department of Chemistry. The project is at the interface of biology, chemistry, physics and computational techniques. The major goal is computational modelling of an enzyme that is a cancer drug target. The student is expected to explore molecular dynamics of the enzyme (protein kinase) in phosphorylated (active) and unphosphorylated (inactive) form. We use hydrogen-deuterium exchange to experimentally measure dynamic differences between two different forms of the enzyme. The knowledge gained from computational modeling, together with the collected experimental data will contribute to understanding process of enzyme activation and it will serve as basis for generation of new more potent cancer therapies. The project is expected to last for 6 – 12 months. If you are interested please contact Nikolina Sekulic (Nikolina.sekulic@ncmm.uio.no).
Literature:
1. Zaytsev AV1, Segura-Peña D2, Godzi M1,3, Calderon A2, Ballister ER2, Stamatov R1, Mayo AM2, Peterson L4,5, Black BE6, Ataullakhanov FI3,7,8, Lampson MA2, Grishchuk EL1. Bistability of a coupled Aurora B kinase-phosphatase system in cell division. Elife. 2016 Jan 14;5:e10644. doi: 10.7554/eLife.10644.