Dr Daryl Shanley
- Email: email@example.com
- Telephone: +44 (0) 191 208 1105
- Fax: +44 (0) 191 208 1101
- Address: Campus for Ageing and Vitality
Institute for Cell and Molecular Biosciences
Newcastle upon Tyne
My research in the biology of ageing has two main branches: one using systems modelling to investigate the mechanisms of ageing the other using dynamic modelling and life history theory to address questions on the evolution of ageing. In each case, I often work in collaboration to share ideas and to obtain high quality data. In systems modelling this is time course data on key molecules generated from cell culture experiments using immunoblotting, microscopy, transcriptomics or proteomics. In life history modelling it is age-structured fertility and mortality data from free living populations. In each branch, I work on the connection between nutritional variation and plasticity in ageing. My long term goal is to merge these two branches and generate predictive models that contain both the mechanisms and their evolutionary basis.
PhD, Computational Biology, University of Manchester
BSc (Hons), Chemistry, University of Bristol.
Senior Lecturer (2010) in Systems Biology of Ageing, Newcastle University.
Director of the Centre for Integrated Systems Biology of Ageing and Nutrition (CISBAN), Newcastle University
Research Associate, Newcastle University.
Research Associate, University of Manchester.
Wellcome Trust Mathematical Biology Prize Studentship, University of Manchester.
Research Scientist, Institut Francais du Petrole, Paris.
Scientist, Exploration and Technical Service, British Gas plc, London.
Current research projects
1) Systems modelling of age-related changes in dermal extra-cellular matrix (further information)
An integrative systems biology project where we measure in-vitro and model in-silico the short-term biochemical network dynamics of extra cellular matrix maintenance (ECM) in populations of young, old and senescent dermal fibroblasts. We have shown in previous work that differences in network dynamics are highly informative and provide a means to identify parts of the network that could be targeted to restore healthy function.
Funded by NC3R and Procter & Gamble.
2) Systems modelling of cell signalling in breast cancer (MESI-STRAT)
The MESI-STRAT consortium explores the interplay of breast cancer metabolism and oncogenic signalling (MEtabolic SIgnaling) by systems medicine approaches. MESI-STRAT develops new models for knowledge-based STRATification of patients into subgroups with different endocrine therapy resistance mechanisms.
Funded by an EU Horizon 2020 consortium grant.
3) Are microRNAs key mediators of cartilage destruction in osteoarthritis?
MicroRNAs are a recently discovered group of factors that control cell behaviour. There are thousands of microRNAs, but specific ones control the behaviour of cartilage cells and have key roles in osteoarthritis. Changing the level of a single microRNA can alter osteoarthritis, but we know that several microRNAs change during disease. We are building computer models of microRNA action in osteoarthritis to identify the outcomes of changing specific microRNAs therapeutically.
Funded by the Dunhill Medical Trust.
4) Harnessing the Power of Big Data to Address the Societal Challenge of Aging (further details)
We are developing computational models to help bridge the laboratory study of ageing cells with measurements from pathology tissue samples. Many human and non-human omics datasets in the public domain provide a rich resource on system-wide changes taking place in different cells across the life course. We will make use of these data together with our own to model the dynamic transition from normal cells to malfunctioning tissues and age-related degenerative diseases.
Funded by the Novo Nordisk Fonden
Module leader for MRes module Biology of Ageing (MMB8011)
Lectures given in modules on Genetics and Human Disease (BMS3010) and Biology of Ageing (BMS2014)
- Martinez Guimera A, Welsh CM, Proctor CJ, McArdle A, Shanley DP. 'Molecular habituation' as a potential mechanism of gradual homeostatic loss with age. Mechanisms of Ageing and Development 2018, 169, 53-62.
- Stamp C, Zupanic A, Sachdeva A, Stoll EA, Shanley DP, Mathers JC, Kirkwood TBL, Heer R, Simons BD, Turnbull DM, Greaves LC. Predominant Asymmetrical Stem Cell Fate Outcome Limits the Rate of Niche Succession in Human Colonic Crypts. EBioMedicine 2018, 31, 166-173.
- Pease LI, Clegg PD, Proctor CJ, Shanley DJ, Cockell SJ, Peffers MJ. Cross platform analysis of transcriptomic data identifies ageing has distinct and opposite effects on tendon in males and females. Scientific Reports 2017, 7(1), 14443.
- King AM, Kirkwood TBL, Shanley DP. Explaining sex differences in lifespan in terms of optimal energy allocation in the baboon. Evolution 2017, 71(10), 2280-2297.
- van den Heuvel J, Zandveld J, Zwaan BJ, Kirkwood TBL, Shanley DP. Growing more positive with age: The relationship between reproduction and survival in aging flies. Experimental Gerontology 2017, 90, 34-42.
- Zandveld J, van den Heuvel J, Mulder M, Brakefield PM, Kirkwood TBL, Shanley DP, Zwaan BJ. Pervasive gene expression responses to a fluctuating diet in Drosophila melanogaster: The importance of measuring multiple traits to decouple potential mediators of life span and reproduction. Evolution 2017, 71(11), 2572-2583.
- Guimera AM, Welsh C, Pezze PD, Fullard N, Nelson G, Roger MF, Przyborski SA, Shanley DP. Systems modelling ageing: From single senescent cells to simple multi-cellular models. Essays in Biochemistry 2017, 61(3), 369-377.
- Pezze PD, Ruf S, Sonntag AG, Langelaar-Makkinje M, Hall P, Heberle AM, Navas PR, van Eunen K, Tolle RC, Schwarz JJ, Wiese H, Warscheid B, Deitersen J, Stork B, Fassler E, Schauble S, Hahn U, Horvatovich P, Shanley DP, Thedieck K. A systems study reveals concurrent activation of AMPK and mTOR by amino acids. Nature Communications 2016, 7, 13254.
- Tomalin LE, Day AM, Underwood ZE, Smith GR, Dalle Pezze P, Rallis C, Patel W, Dickinson BC, Bähler J, Brewer TF, Chang CJ-L, Shanley DP, Veal EA. Increasing extracellular H2O2 produces a bi-phasic response in intracellular H2O2with peroxiredoxin hyperoxidation only triggered once the cellular H2O2-buffering capacity is overwhelmed. Free Radicals in Biology and Medicine 2016, 95, 333-348.
- Zupanic A, Meplan C, Huguenin GVB, Hesketh JE, Shanley DP. Modeling and gene knockdown to assess the contribution of nonsense-mediated decay, premature termination, and selenocysteine insertion to the selenoprotein hierarchy. RNA 2016, 22(7), 1076-1084.
- Thomas MG, Shanley DP, Houston AI, McNamara JM, Mace R, Kirkwood TBL. A dynamic framework for the study of optimal birth intervals reveals the importance of sibling competition and mortality risks. Journal of Evolutionary Biology 2015, 28(4), 885-895.
- Barter MJ, Tselepi M, Gomez R, Woods S, Hui W, Smith GR, Shanley DP, Clark IM, Young DA. Genome-wide microRNA and gene analysis of mesenchymal stem cell chondrogenesis identifies an essential role and multiple targets for miR-140-5p. Stem Cells 2015, 33(11), 3266-3280.
- Dolan DWP, Zupanic A, Nelson G, Hall P, Miwa S, Kirkwood TBL, Shanley DP. Integrated Stochastic Model of DNA Damage Repair by Non-homologous End Joining and p53/p21- Mediated Early Senescence Signalling. PLoS Computational Biology 2015, 11(5), e1004246.
- Zupanic A, Méplan C, Grellscheid SN, Mathers JC, Kirkwood TBL, Hesketh J, Shanley D. Detecting translational regulation by change point analysis of ribosome profiling data sets. RNA 2014, 20(10), 1507-1518.
- Dalle Pezze P, Nelson G, Otten EG, Korolchuk VI, Kirkwood TBL, von Zglinicki T, Shanley DP. Dynamic Modelling of Pathways to Cellular Senescence Reveals Strategies for Targeted Interventions. PLoS Computational Biology 2014, 10(8), e1003728.
- van den Heuvel J, Zandveld J, Mulder M, Brakefield PM, Kirkwood TBL, Shanley DP, Zwaan BJ. The plastic fly: the effect of sustained fluctuations in adult food supply on life-history traits. Journal of Evolutionary Biology 2014, 27(11), 2322-2333.
- Smith GR, Shanley DP. Computational modelling of the regulation of Insulin signalling by oxidative stress. BMC Systems Biology 2013, 7, 41.
- Dolan D, Nelson G, Zupanic A, Smith G, Shanley D. Systems Modelling of NHEJ Reveals the Importance of Redox Regulation of Ku70/80 in the Dynamics of DNA Damage Foci. PLoS One 2013, 8(2), e55190.
- van den Heuvel J, Saastamoinen M, Brakefield PM, Kirkwood TBL, Zwaan BJ, Shanley DP. The Predictive Adaptive Response: Modeling the Life-History Evolution of the Butterfly Bicyclus anynana in Seasonal Environments. American Naturalist 2013, 181(2), E28-E42.
- Dalle Pezze P, Sonntag AG, Thien A, Prentzell MT, Godel M, Fischer S, Neumann-Haefelin E, Huber TB, Baumeister R, Shanley DP, Thedieck K. A Dynamic Network Model of mTOR Signaling Reveals TSC-Independent mTORC2 Regulation. Science Signaling 2012, 5(217), ra25.
- Sonntag AG, Pezze PD, Shanley DP, Thedieck K. A modelling-experimental approach reveals insulin receptor substrate (IRS)-dependent regulation of adenosine monosphosphate-dependent kinase (AMPK) by insulin. FEBS Journal 2012, 279(18), 3314-3328.
- Sonntag AG, Dalle Pezze P, Shanley DP, Thedieck K. A modelling–experimental approach reveals insulin receptor substrate (IRS)-dependent regulation of adenosine monosphosphate-dependent kinase (AMPK) by insulin. FEBS Journal 2012, 279(18), 3314-3328.
- Lawless C, Jurk D, Gillespie CS, Shanley D, Saretzki G, von Zglinicki T, Passos JF. A Stochastic Step Model of Replicative Senescence Explains ROS Production Rate in Ageing Cell Populations. PLoS One 2012, 7(2), e32117.
- Rashidi A, Kirkwood TBL, Shanley DP. Evolution of Asymmetric Damage Segregation: A Modelling Approach. In: Breitenbach, M., Jazwinski, S.M. Laun, P, ed. Aging Research in Yeast. Berlin; New York: Springer, 2012, pp.315-330.
- Cole-Ezea P, Swan D, Shanley D, Hesketh J. Glutathione Peroxidase 4 has a major role in protecting mitochondria from oxidative damage and maintaining oxidative phosphorylation complexes in gut epithelial cells. Free Radical Biology and Medicine 2012, 53(3), 488-497.
- Dalle Pezze P, Sonntag AG, Shanley DP, Thedieck K. Response to Comment on "A Dynamic Network Model of mTOR Signaling Reveals TSC-Independent mTORC2 Regulation": Building a Model of the mTOR Signaling Network with a Potentially Faulty Tool. Science Signaling 2012, 5(232), lc4.
- Kirkwood TBL, Shanley DP. The connections between general and reproductive senescence and the evolutionary basis of menopause. In: Annals of the New York Academy of Sciences: Reproductive Aging. 2010, Georgetown University, Washington, DC, USA: Wiley-Blackwell Publishing, Inc.
- Rashidi A, Kirkwood TBL, Shanley DP. Metabolic evolution suggests an explanation for the weakness of antioxidant defences in beta-cells. Mechanisms of Ageing and Development 2009, 130(4), 216-221.
- Proctor CJ, Lydall D, Boys RJ, Gillespie CS, Shanley D, Wilkinson DJ, Kirkwood TBL. Modelling the checkpoint response to telomere uncapping in budding yeast. Journal of the Royal Society Interface 2007, 4(12), 73-90.
- Shanley DP, Sear R, Mace R, Kirkwood TBL. Testing evolutionary theories of menopause. Proceedings of the Royal Society B: Biological Sciences 2007, 274(1628), 2943-2949.
- Shanley DP, Kirkwood TBL. Caloric restriction does not enhance longevity in all species and is unlikely to do so in humans. Biogerontology 2006, 7(3), 165-168.
- Gillespie C, Wilkinson D, Proctor CJ, Shanley D, Boys RJ, Kirkwood TBL. Tools for the SBML community. Bioinformatics 2006, 22(5), 628-629.
- Kirkwood TBL, Boys RJ, Gillespie CS, Proctor CJ, Shanley DP, Wilkinson DJ. Computer Modeling in the Study of Aging. In: Austad, S.N., Masoro, E.J, ed. Handbook of the Biology of Aging. Amsterdam; Boston: Academic Press, 2005, pp.334-359.
- Kirkwood TBL, Shanley DP. Food restriction, evolution and ageing. Mechanisms of Ageing and Development 2005, 126(9), 1011-1016.
- Proctor CJ, Soti C, Boys RJ, Gillespie CS, Shanley DP, Wilkinson DJ, Kirkwood TBL. Modelling the actions of chaperones and their role in ageing. Mechanisms of Ageing and Development 2005, 126(1), 119-131.
- Gillespie CS, Proctor CJ, Shanley DP, Wilkinson DJ, Boys RJ, Kirkwood TBL. Web-services for the biology community: the BASIS project. In: UK e-Science All Hands Meeting. 2005, Nottingham, UK.
- Gillespie C, Proctor CJ, Boys R, Shanley D, Wilkinson D, Kirkwood T. A mathematical model of ageing in yeast. Journal of Theoretical Biology 2004, 229(2), 189-196.
- Kirkwood TBL, Boys RJ, Gillespie CJ, Proctor CJ, Shanley DP, Wilkinson DJ. Towards an e-biology of ageing: Integrating theory and data. Nature Reviews Molecular Cell Biology 2003, 4(3), 243-249.
- Shanley DP, Kirkwood TBL. Caloric restriction, life-history evolution, and bioenergetics: Response to Mitteldorf. Evolution 2001, 55(9), 1906.
- Shanley DP, Kirkwood TBL. Evolution of the human menopause. BioEssays 2001, 23(3), 282-287.
- Sear R, Shanley D, Mcgregor IA, Mace R. The fitness of twin mothers: Evidence from rural Gambia. Journal of Evolutionary Biology 2001, 14(3), 433-443.
- Kirkwood TBL, Shanley DP. Caloric restriction, hormesis and life history plasticity. Human and Experimental Toxicology 2000, 19(6), 338-339.
- Kirkwood TBL, Shanley DP. Caloric restriction, hormesis and life-history plasticity. BELLE Newsletter 2000, 8(3).
- Shanley DP, Kirkwood TBL. Calorie Restriction and Aging: A Life-History Analysis. Evolution 2000, 54(3), 740-750.
- Kirkwood TBL, Kapahi P, Shanley DP. Evolution, stress, and longevity. Journal of Anatomy 2000, 197, 587-590.
- Kirkwood, T.B.L., Adams, C., Gibbons, L., Hewitt, C.D., Kapahi, P., Kowald, A., Leeming, G., Lithgow, G.J., Martin, K., Potten, C.S., Shanley, D.P. Cell maintenance and stress response in ageing and longevity. In: Rattan, S.I.S., Toussaint, O, ed. Molecular Gerontology. New York: Plenum Press, 1996, pp.193-200.