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T B L Kirkwood

Publications and source records attributed to T B L Kirkwood.

5 recordsLinked to original sources
PubMed2007

Modelling the checkpoint response to telomere uncapping in budding yeast.

One of the DNA damage-response mechanisms in budding yeast is temporary cell-cycle arrest while DNA repair takes place. The DNA damage response requires the coordinated interaction between DNA repair and checkpoint pathways. Telomeres of budding yeast are capped by the Cdc13 complex. In the temperature-sensitive cdc13-1 strain, telomeres are unprotected over a specific temperature range leading to activation of the DNA damage response and subsequently cell-cycle arrest. Inactivation of cdc13-1 results in the generation of long regions of single-stranded DNA (ssDNA) and is affected by the activity of various checkpoint proteins and nucleases. This paper describes a mathematical model of how uncapped telomeres in budding yeast initiate the checkpoint pathway leading to cell-cycle arrest. The model was encoded in the Systems Biology Markup Language (SBML) and simulated using the stochastic simulation system Biology of Ageing e-Science Integration and Simulation (BASIS). Each simulation follows the time course of one mother cell keeping track of the number of cell divisions, the level of activity of each of the checkpoint proteins, the activity of nucleases and the amount of ssDNA generated. The model can be used to carry out a variety of in silico experiments in which different genes are knocked out and the results of simulation are compared to experimental data. Possible extensions to the model are also discussed.

Cell Cycle↗
PubMed2002

The Institute for Ageing and Health, University of Newcastle, UK.

The Institute For Ageing And Health (IAH) is the largest cross-disciplinary research grouping within Newcastle University's Faculty of Medicine, which recently obtained the highest 5 or 5* ratings in all fields evaluated in the UK Research Assessment Exercise 2001. The IAH was set up in 1994 to bring together clinical, basic and social scientists in partnership with colleagues in the National Health Service. It builds upon a long tradition of outstanding clinical research on age-related disorders, particularly in the field of dementia where the pioneering studies of Tomlinson and Roth in the 1960s first showed Alzheimer's disease to be the commonest cause of cognitive decline in later life. The clinical research of the IAH now extends to both neurodegenerative and vascular dementia in a joint Medical Research Council-University Development for Clinical Brain Ageing, and to studies in many other areas including depression in later life, falls and neurovascular instability, stroke and ischaemic brain disease, and health services research on the medical and social care of older people. These diverse areas of clinical investigation are now complemented by strong research on the basic biology of ageing within the new Department of Gerontology with its programmes on the genetics of ageing and longevity; molecular mechanisms of cellular ageing, including oxidative stress, DNA damage and genomic instability, telomere reduction and regulation, mitochondrial DNA mutations, and accumulation of aberrant proteins; and theoretical models of the ageing process. An ambitious strategy for future research on ageing and age-related disorders is based on the synergy between these complementary approaches.

Aging↗
PubMed2002

Molecular gerontology.

Evolutionary theory and empirical evidence from many lines of research suggest that ageing is a process of gradual accumulation of damage in cells and tissues of the body, leading eventually to frailty and increased risk from a spectrum of age-associated diseases. There are multiple kinds of damage that affect cells, ranging from mutations in DNA to oxidative attack on proteins by chemical by-products of normal cellular metabolism. In some ways the surprising thing is not that we age, but that we live as long as we do. The key to understanding longevity lies in the network of cell maintenance systems that cooperate to slow the accumulation of damage. Research has shown that long-lived species carry out cellular maintenance better than short-lived species, suggesting that enhancement of the body's natural maintenance systems may postpone aspects of ageing. Recognition that ageing results from accumulation of damage also points to a role for lifestyle interventions (e.g. nutrition and exercise) to help prevent damage or promote repair.

Aging↗