Master Student Biology/ Biomedics/ Biotechnology
Your function within the department
7-9 months rotation for master student biology/biomedics/biotechnology at the division of Cell Biology, NKI/AvL, Amsterdam
From meters to nanometers: Using super resolution imaging to visualize condensed DNA
When cells divide, it is crucial that the two newly formed daughter cells harbour the exact same genetic material as their mother cell. It is quite a challenge for dividing cells to separate the several-meters long DNA threads without any errors. To achieve this, cells condense their long threads of DNA into short and compact structures that are only few microns in length. This condensation is essential for faithful segregation of DNA but the responsible mechanism(s) are still a big mystery.
Condensin is an ATPase enzyme that is known to drive the DNA condensation process. The condensin complex consists of five proteins, which together form a gigantic ring-shaped structure that can entrap DNA threads. One model of how condensin confers condensation is by forming and stabilizing long DNA loops inside its ring, thereby bringing distant parts of the chromosome closely together. Through the formation of many consecutive loops, DNA threads would thus become condensed. In this project we aim to visualize DNA and condensin by optical super resolution (SR) microscopy https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2014/press.html
In SR microscopy the diffraction limit which hampers conventional fluorescence microscopy is circumvented and thereby a resolution up to ~10 nm can be achieved. The first goal is to optimize SR microscopy of DNA and condensin in fixed cells. We will then study how condensed DNA is shaped and the localization of condensin on condensed DNA. We will make use of a number of different condensin variants that either impair or enhance the condensation process. Comparing those different variants of condensin by super resolution might provide valuable insights into how DNA condenses.
In this project, the groups of Dr B. Rowland and Prof. Dr. K. Jalink, both at the division of Cell Biology, team up. Techniques used include: cell culture / transfections / confocal microscopy / SR microscopy / computer image analysis.