Research

My research interests and a summary of the projects I have participated in

Ageing is a major risk factor for a variety of diseases, yet little is known about its molecular nature. Since the beginning of my research career I’ve been involved in several projects, mainly to understand molecular characteristics of ageing, pharmacological interventions that can reverse its effects, and the link between ageing and age-related diseases. While the questions I am interested in are quite biological, I am also interested in the development and application of bioinformatic, statistical or machine learning algorithms that can best address these questions.

Anti-aging drug studies

The studies in model organisms have shown that, ageing and ageing-related functional deterioration can be slowed down and even can be prevented through genetic, environmental or chemical perturbations. Gaining motivation from these studies, we have conducted several studies to identify potential ageing-modulator drugs in humans. Using drug repurposing (i.e. finding new applications for the drugs used for other conditions) approaches, we have published two studies to find drug that can 1) target ageing-related genes1 and 2) target gene expression changes that occur during ageing2. Further, we experimentally validated one of the drugs identified by both of these studies, Tanespimycin, using C.elegans as a model. In a review article3, we have recently summarised the available computational studies and the future directions in this area. Apart from identifying new drugs, we also focus on the testability of these drugs in model organisms. The questions we ask is: “Assuming we find an anti-ageing drug for humans. Before clinical trials, which model organism could be used to test the anti-ageing effects of this drug?”. In order to answer this question, utilizing several parameters such as drug-protein interaction, evolutionary and structural conservation of the target protein between the model organisms and humans, availability of the drug we calculate a score for different model organisms. This study is still ongoing and stems from another study developed by a previous postdoc in our lab4.

[1] Fuentealba, M., Dönertaş, H. M., Williams, R., Labbadia, J., Thornton, J. M., & Partridge, L. (2019). Using the drug-protein interactome to identify anti-ageing compounds for humans. PLOS Computational Biology, 15(1), e1006639. https://doi.org/10.1371/journal.pcbi.1006639

[2] Dönertaş, H. M., Fuentealba Valenzuela, M., Partridge, L., & Thornton, J. M. (2018). Gene expression-based drug repurposing to target aging. Aging Cell, 17(5), e12819. https://doi.org/10.1111/acel.12819

[3] Dönertaş, H. M. (eq), Fuentealba, M. (eq), Partridge, L., & Thornton, J. M. (2019). Identifying Potential Ageing-Modulating Drugs In Silico. Trends in Endocrinology & Metabolism, 30(2), 118–131. https://doi.org/10.1016/j.tem.2018.11.005

[4] Ziehm, M., Kaur, S., Ivanov, D. K., Ballester, P. J., Marcus, D., Partridge, L., & Thornton, J. M. (2017). Drug repurposing for aging research using model organisms. Aging Cell, 16(5), 1006–1015. https://doi.org/10.1111/acel.12626

Molecular characteristics of ageing

  • What are the changes in gene expression during ageing, when compared to development? Are they continuation or reversal of the changes in development? Publication
  • How interindividual variability of gene expression changes with age? What is the effect of preprocessing methods commonly used for gene expression analysis on the interpretation of these age-related variability changes? Publication
  • Investigation of mutation accumulation theory of ageing, analysing the changes in gene expression with age in multiple mammalian species & tissues Publication

Other studies that I’ve conducted or contributed

  • Investigation of gene flow events during the Neolithic transition in West Eurasia through ancient DNA analysis Publication
  • Neanderthal Introgression in Western Asia Publication
  • Demographic investigation of first farmers in Anatolia, through ancient DNA analysis Publication
  • Characterisation of the reactions associated with multi-reaction enzymes in the Enzyme Classification (EC) System Publication

You can find my up-to-date publication list in Google Scholar.