Introduction to me and my research!
My name is Olivia Grant, a 2nd year PhD candidate at the University of Essex and the Queen Mary University of London. I graduated with my BSc in Biomedicine from the University of Essex! During my third year at Essex, I completed my final year undergraduate project in Dr. Radu Zabet’s laboratory performing a bioinformatic analysis of TF binding within the human genome. This project initiated my interest in the use of computational methods for studying biological systems. Prior to this, I often worried about my career as a scientist as I knew I did not particularly enjoy wet lab work, so when I discovered the power of using computational power to answer significant biological questions, I was hooked! I am now doing my PhD in Radu Zabet’s lab in collaboration with the Institute for Social and Economic Research at Essex.
My research interests focus on epigenetics, mainly DNA methylation. My primary interest is trying to understand how the environment influences our epigenome. The association of the environment with health has been widely recognized and there is well-documented evidence inferring a link between air pollution exposure and a global increase in mortality and morbidity. Approximately 7 million deaths each year have been attributed to exposure to air pollution due to the sequential onset of diseases such as asthma, cardiovascular disease, stroke, and the development of malignancies following exposure. The molecular mechanisms by which this association occurs are yet to be delineated, throughout my research, I hope to investigate whether epigenetic processes underlie this association.
My research interests focus on epigenetics, mainly DNA methylation. My primary interest is trying to understand how the environment influences our epigenome. The association of the environment with health has been widely recognised and there is well documented evidence inferring a link between air pollution exposure and a global increase in mortality and morbidity. Approximately 7 million deaths each year have been attributed to exposure to air pollution due to the sequential onset of diseases such as asthma, cardiovascular disease, stroke and the development of malignancies following exposure. The molecular mechanisms by which this association occurs is yet to be delineated, throughout my research, I hope to investigate whether epigenetic processes underlie this association.
What is epigenetics?
Epigenetics, a term first coined by Waddington in 1942 means ‘above’ or ‘on top of’ genetics. Waddington developed a metaphorical epigenetic landscape to provide modern-day scientists with a powerful, yet simple way of thinking (Fig.1). Epigenetics is defined as mitotically heritable changes which correlate with gene expression and consequently protein expression (Jaenisch and Bird, 2003). This ultimately leads to genes being ‘switched on and off’, a process that is crucial for cellular activities such as differentiation. Epigenetic changes do not alter the primary DNA sequence itself, and there are three main epigenetic regulators; DNA methylation, histone modifications, and non-coding RNA’s. Exploring these markers enables investigations into the relationship between epigenetics and a range of disorders. These markers are flexible and can be altered in response to several environmental factors such as air pollution, smoking, and physical activity level (Alegría-Torres, Baccarelli and Bollati, 2011). These epigenetic hallmarks have potential to provide biomarkers and act as indicators of exposure, allowing identification of vulnerable populations.
The widely studied epigenetic mark: DNA methylation
DNA methylation is the most quintessential epigenetic modification, and it involves the addition of a methyl group to the fifth carbon of a cytosine base. DNA methylation occurs predominantly on cytosines proximal to a guanine base, commonly referred to as CpG sites. The majority of CpG sites within the genome are methylated and generally induce transcriptional repression upon interaction with histone modifications and non-coding RNAs, and is essential for silencing retroviral elements, genomic imprinting, and X chromosome inactivation (Moore et al., 2012). However, levels of modified cytosine vary largely across cell types and genomic locations and are not always located within CpG sites, non CpG methylation has previously been identified in the plants, brain tissues, and embryonic stem cells (Catoni et al., 2018).
The relationship between DNA methylation and gene expression remains poorly understood, with elevated gene body DNAm being attributed to active expression (Wagner et al., 2014) and hypermethylation within enhancers and promoters leading to stable transcriptional silencing (Ehrlich and Lacey, 2013). Exposure to air pollution has been demonstrated to impact our epigenome, and more specifically to alter our DNA methylation patterns (Rider and Carlsten, 2019).
What do we really mean when we say, ‘air pollution’?
Ambient air pollution is a combination of gaseous components such as sulphates, nitrogen oxides, benzene, and particulate matter. Air pollution is typically divided into two categories; outdoor air pollution and indoor air pollution. Outdoor air pollution arises from sources such as the burning of fossil fuels, ground-level ozone, tobacco smoke, and gases such as nitrogen oxides, sulphur dioxide, and carbon monoxide (CO). Fossil fuel combustion, primarily from TRAP (traffic-related air pollution) in urban environments is the major source of ambient air pollution (Kelly and Fussell, 2015).
The majority of morbidity associated with pollution is thought to be due to a pollutant called PM2.5 which is composed of nitrates, ammonia, sodium chloride, black carbon, mineral dust, and water. Particulate matter can be of varying sizes (including PM10) and due to their incredibly small aerodynamic diameters, they are able to lodge deep into the alveoli of the lungs, and at their smallest size even penetrate the lung epithelium where they can then enter the bloodstream.
The exact mechanisms by which exposure to pollution affects our health remains obscure and further work is necessary to clarify pathways involved in health defects that are observed with both short- and long-term exposure to air pollution. Nevertheless, there are many other lifestyle factors (smoking status, diet, physical activity) that should be considered when analyzing exposure following their implications on health (Alegría-Torres et al., 2011). The biggest gap in this area of research is the lack of consideration for several environmental factors and furthermore, the interplay of these factors on altering DNA methylation signatures. Something I hope to fill within my research and time in my PhD!
I hope to complete my PhD within the next two years and following this, I aspire to begin a post-doctoral position continuing my research into DNA methylation/ epigenetic research. I really enjoy science communication, so I hope to also continue my sci-comm journey and maybe one day start a YouTube channel!
- Alegría-Torres, J., Baccarelli, A. and Bollati, V. (2011). Epigenetics and lifestyle. Epigenomics, 3(3), pp.267-277.
- Alegría-Torres, J., Barretta, F., Batres-Esquivel, L., Carrizales-Yáñez, L., Pérez-Maldonado, I., Baccarelli, A. and Bertazzi, P. (2013). Epigenetic markers of exposure to polycyclic aromatic hydrocarbons in Mexican brickmakers: A pilot study. Chemosphere, 91(4), pp.475-480.
- Bird, A., Taggart, M., Frommer, M., Miller, O. and Macleod, D. (1985). A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell, 40(1), pp.91-99.
- Catoni, M., Tsang, J., Greco, A. and Zabet, N. (2018). DMRcaller: a versatile R/Bioconductor package for detection and visualization of differentially methylated regions in CpG and non-CpG contexts. Nucleic Acids Research.
- Ehrlich, M. and Lacey, M., 2013. DNA methylation and differentiation: silencing, upregulation and modulation of gene expression. Epigenomics, 5(5), pp.553-568.
- Jaenisch, R. and Bird, A. (2003). Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nature Genetics, 33(S3), pp.245-254.
- Kelly, F. and Fussell, J. (2015). Air pollution and public health: emerging hazards and improved understanding of risk. Environmental Geochemistry and Health, 37(4), pp.631-649.
- Rider, C. and Carlsten, C., 2019. Air pollution and DNA methylation: effects of exposure in humans. Clinical Epigenetics, 11(1).