New paper

How cells maintain normal chromosome numbers ?

Cell division is an essential process in humans, animals and plants; dying or injured cells are continuously replenished throughout life. When cell division goes wrong, it can lead to a range of diseases, such as cancer, and problems with fertility and development, including babies born with the wrong number of chromosomes as in Down's syndrome. 

How can irregular numbers of chromosomes arise? When a mother cell prepares to divide into two daughter cells, rope-like structures called microtubules capture chromosomes and pull them apart into two equal sets. This step of separating chromosomes is very important because any error in the separation process will lead to incorrect numbers of chromosomes in the two daughter cells. 


Roshan and Duccio - two Ph.D. students in my research group - led a fantastic project using high-resolution microscopy techniques to uncover master regulators of an important step in chromosome segregation. They show that chromosomes captured along microtubule-walls require two proteins - Aurora-B and BubR1-bound phosphatase - for bringing the chromosome to microtubule-ends. When this step fails,  separation of chromosomes cannot begin. 

Chromosomes attach to microtubules at a special site called kinetochore. The kinetochore is a multiprotein platform (shown in red) that is predominatly captured along the walls of microtubules (shown in green). The step-wise process by which kinetochores tethered to microtubule-walls are brought to microtubule-ends is called end-on conversion (cartoon below). Our new paper uncovers the first set of master regulators of the end-on conversion process in human cells.

End-on Conversion: Kinetochore tethered to microtubule (MT)-wall becomes tethered to MT-end

We are looking forward to identify the precise molecular roles of these two master regulators in the end-on conversion process, so that we can discover the molecular switches that ensure accurate chromosome numbers.

How is this discovery clinically useful?
Clinicians who treat cancers are often faced with aggressive forms of the disease where cells display irregular numbers of chromosomes. They could potentially test for changes in levels of these two master regulators to understand the underlying reason for irregular chromosome numbers. This will inturn help them choose the right kind of drug for the individual. Thus, understanding the intricate mechanisms that normal cells use to maintain chromosome numbers is crucial to understand why they go wrong in diseases.

For the actual paper and how they discovered this, click here: 
https://www.nature.com/articles/s41467-017-00209-z
Image: Duccio, Revathy and Maddy (Draviam group members in the microscope room at Queen Mary University of London).
Our lab website: 
http://www.draviamlab.uk/