Morrison Group

General overview

Changes in the genetic makeup of cells are one of the key differences between cancer cells and normal cells.  Instability in the genome is believed to be a key early event in cancer development.  Cells normally divide in only two directions, so that each daughter cell gets the right genetic material, which is exactly half of the chromosomes.  A structure called the centrosome controls this process. 

Dividing cells have two centrosomes that act as opposite poles and draw the dividing chromosomes toward them.  Cancer cells have multiple centrosomes, causing uneven cell division.  Centrosomal problems also play roles in developmental disorders.  Finally, several centrosome components are involved in anchoring the cilium, a tail-like extension that senses and responds to the cellular environment, and problems in these components give rise to a complex class of diseases known as ciliopathies.

Dissection of the mechanisms controlling centrosome number

Centrosomes are complex organelles and contain some distinctive substructures.  We hypothesise that these substructures have distinct roles in controlling cell division.  We use reverse genetics to disrupt the genes that code for key elements of the individual parts of the centrosomes.  We then examine how cells divide, form centrosomes, manage their chromosomes and carry out activities that maintain genome stability.

Electron micrograph of the centrosome and mitotic chromosomes in a DT40 cell   (Pic. Tiago Dantas).	Amplified centrosomes in an untreated (left) and an irradiated U2OS osteosarcoma cell (right) Centrosomes are in red/ green, DNA in blue.   (Pic. Emer Bourke).	Primary cilium (red) in a human RPE1 cell.  Centrin is shown in green, DNA in blue (Pic. Pauline Conroy).

Current interests

Centrosomes play important roles in mitosis, establishing the bipolar mitotic spindle.  Centrosome abnormalities have long been implicated in mitotic aberrations, leading to problems in chromosome segregration, aneuploidy and genomic instability.  Experiments in Drosophila have demonstrated that centrosome amplification can cause metastatic tumour formation.  Cell cycle regulation is another important activity of the centrosome.  Centrosomes are also critical for ensuring appropriate stem cell division and for allowing cilium formation, so that developmental disorders and ciliopathies result from centrosome abnormalities. 

At present, we are focussing on centrosome components that are also involved in DNA repair and cell cycle checkpoints.  Microcephalin ( MCPH1) and pericentrin ( PCNT) are involved in brain development and cell cycle signalling.  Primary microcephaly and premature chromosome condensation are diseases associated with mutations in MCPH1, which has also been implicated as a tumour suppressor.  A form of primordial dwarfism is associated with PCNT mutations and PCNT is a putative oncogene.  Centrins and Cep164 are associated with nucleotide excision repair genes that repair UV-mediated DNA damage.  Centrosome cohesion is maintained by C-Nap1 and rootletin, with the control of centriole association being regulated by separase and Plk1.

These different research strands are aimed at understanding the key mechanisms that ensure that cells keep their genomes intact.   This understanding will allow us to see how certain genes are involved in causing cancer and may allow us to identify particular targets that may be worth targeting with drugs to try and kill tumour cells.

Lab members

Lab retreat, showcasing the weather, Furbo, Co. Galway, October 2008. Left to right: Anna, Tiago, Emer, Pauline, Yi-fan, Chiara, James, Burcu, Helen, Maciek, Carol.
Members of the group in Yosemite National Park, after presenting their work at the American Society for Cell Biology Annual Meeting in San Francisco, December 2005. L-R, Helen, Ciaran, Liam, Emer and Anna.

Funding

Work in the lab is funded by Science Foundation Ireland. http://www.sfi.ie/

Positions available

Openings for postdoctoral fellows with interests/ experience in DNA repair and chromosome biology and for students with similar interests arise sporadically. Please contact Ciaran Morrison at ciaran.morrisonnuigalway.ie for further details.

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