Chromosome segregation

AndrewResearch Summary

It has been known for over 100 years that an abnormal number of chromosomes (aneuploidy) is a hallmark of cancer. We now know that aneuploidy, caused by errors in chromosome segregation, can cause cancer. We are therefore focused on trying to understand how the coupled mechanical system of chromosomes, kinetochores, spindle poles, microtubules and molecular motors are able to self-organize into the mitotic spindle and accurately segregate sister chromatids in anaphase.

 

We are particularly interested in deciphering how kinetochores – multiprotein mechanochemical machines – form strong, but flexible attachments to the dynamic plus-end of spindle microtubules and generate the forces necessary to power chromosome movement. We expect this programme of fundamental science to lead to a better understanding of how aneuploidy occurs and identify new targets for anti-cancer treatment.

 

Andrew McAinsh

 

>> see what happened to past members of the lab here

 

>> 2-page cv available here

 

>> current collaborations coming soon...

 

>> image gallery coming soon...

 

Selected Publications

 

Amaro, A.C., Samora, C.P., Holtackers, R., Wang, E., Kingston, I., Alonso, M., Lampson, L., †McAinsh, A.D. and †Meraldi, P. (2010)
Molecular control of kinetochore-microtubule dynamics and chromosome oscillation
Nature Cell Biology, 12: 319-329

 

*Jaqaman, K., *King, E., *Amaro, A.C., *Winter, J.R., Dorn, J.F., Elliott, H.L., Mchedlishvili, N., McClelland, S.E., Porter, I.M., Posch, M., Toso, A., †Danuser, G., †McAinsh, A.D., †Meraldi, P., †Swedlow, J.R. (2010)
Kinetochore alignment within the metaphase plate is regulated by centromere stiffness and microtubule depolymerases
Journal of Cell Biology, 188: 665-79

 

Braun, M., Drummond, D.R., Cross, R.A. & McAinsh, A.D. (2009)
Klp2 organises microtubules into parallel bundles by an ATP-dependent sorting mechanism
Nature Cell Biology, 11: 724-730

*Toso, A., *Winter, J., Garrod, A.J., Amaro, A.C., †Meraldi, P. and †McAinsh, A.D. (2009)
Kinetchore-generated pushing forces separate centrosomes during bipolar spindle assembly.
Journal Cell Biology, 184: 365-372

*McClelland, S.E., *Borusu, S., Amaro, A.C., Winter, J.R., Belwal, M., †McAinsh, A.D. and †Meraldi, P. (2007)
The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity.
EMBO J., 26: 5033-5047

lab members & projects

AinslieAinslie Garrod | research assistant | funded by Marie Curie Cancer Care

Recently we identified a new human kinetochore protein, DIMP, which controls mictotubule dynamics at kinetochores. I am now determining the biochemical properties of DIMP. I am also working towards developing new live-cell imaging assays to follow microtubule and kinetochore dynamics

CaterinaCatarina Samora | phd student | funded by Fundação para a Ciência ea Tecnologia

My aim is to understand how kinetochore microtubule dynamics is regulated and how perturbations in this system affect the formation of a bipolar spindle and a stable metaphase plate. I’m using a RNAi-based approach in combination with several in vitro and in vivo techniques to address this question.

CaterinaElina Vladimirou | research fellow | funded by Marie Curie Cancer Care

I am interested in understanding the mechanics which control chromosome directional instability during metaphase and anaphase using live-cell imaging and computational tools.

 

funding sources

Programe Grant | Marie Curie Cancer Care
Mechanisms of chromsosome segregation
£705,000 - 2009 to 2012

PhD fellowship | Fundação para a Ciência ea Tecnologia
Functional analysis of CENP-A NAC/CAD
£130,000 - 2008 to 2012