Responses to DNA damage in human cells

Ongoing research areas include the characterisation of DNA damage response pathways in human mesenchymal stem cells, in collaboration with the Regenerative Medicine Institute at NUI, Galway, and characterisation of responses to novel derivatives of the anti-cancer drug mitomycin C in normal and Fanconi anemia cell lines (in collaboration with Dr. F. Aldabbagh, School of Chemistry, NUI, Galway).

Chromatin structure and function

Our aim is to understand the chromatin structure-function relationship in molecular detail. We are working to determine its molecular motions using recombinantly produced nucleosomes and a variety of biochemical and biophysical assays.

Trinucleotide repeat instability and mutagenesis

We study the genetic mechanisms of mutagenesis and repair at trinucleotide repeats. We continue to identify yeast proteins that either inhibit or promote triplet repeat expansions, using genetic and biochemical approaches. Once known, we look at human homologs of these yeast proteins to see if they function analogously in cultured cells of the human CNS.

Eukaryotic DNA damage responses

We investigate the mechanisms of sensing and responding to DNA damage. Our research is a balance of hypothesis and discovery-led research using both genetic and biochemical approaches to analyse the role of checkpoint mediators, the central protein kinase regulators and the epigenetic regulation of the DDR.

Gene expression and nuclear structure

Our aims are to elucidate the chromosomal context of NORs and determine how their structure facilitates nucleolar formation and co-ordination of multiple steps in rRNA maturation. This work has additional significance as control of ribosome biogenesis is intimately connected to cellular growth and proliferation and is disregulated in many human diseases including cancer.

DNA damage response and mitosis

Our research investigates how DNA damage is signalled to the centrosome duplication apparatus and defines the impact this has on proliferating cells. Other ongoing projects include the analysis of the Smc5/6 complex in DNA repair and the dissection of the activities of Mcph1 microcephalin.

DNA replication control in the eukaryotic cell cycle

We analyse the activity of the replication and regulatory proteins and the posttranslational modifications and protein-protein interactions that control them. We have also investigated the functions of certain proteins in the cell cycle after DNA damage and studied the life cycle of the human polyoma virus BKV after kidney transplantations.

Epigenetic regulation of gene expression

To better understand epigenetic mechanisms in the regulation of gene expression, we are studying the human MOF complex in cultured human cells and tumour cell lines.  Studying hMOF and H4K16 acetylation allows us to investigate the role of this particular modification in normal development and its involvement in cancer development.

DNA replication and anticancer therapeutics

Our lab is interested in studying the mechanisms that regulate DNA replication in human cancer cells with particular emphasis on the Cdc7 kinase. These studies will impact on our basic understanding of genome duplication, providing key insights into its mechanistics and regulation.

Chromosome inheritance and mitosis

We are studying the basis of chromatin-directed inheritance in human cells by dissecting the pathway for centromere assembly in human cells. Efforts are focused on understanding the regulation of an ensemble of ~15 genes coding for CENP-A and a number of other constitutive CENPs, identifying which of those proteins are heritable in situ and when they are assembled.

Microscopy

Confocal microscopes
Scanning electron microscope with EDX
Transmission electron microscope
Scanning probe atomic force microscope
Flow cytometry
Analysis and cell sorting capabilities using FACS ARIA II, FACS ARIA-I, FACScalibur and FACSCanto II

Mass spectrometry

The mass spectrometry system managed by NCBES consists of GCT and QTOF high-resolution mass spectrometers. This state of the art facility offers researchers the ability to obtain high resolution mass spectral data by GC-MS, LC-MS, direct infusion or by direct insertion of a solid sample.

Cell culture and fermentation

A number of modern cell culture suites rated at safety class I and II are located in the centre.
A fermentation facility in the Department of Biochemistry provides the capability for continuous growth and large batch production of biomass.