Website Queen's University Belfast
Overview
Bisphenol-A (BPA) is a chemical building block used to strengthen polycarbonate plastic products [1], that binds and activates the estrogen receptors (ESR1 and ESR2) [2,3]. Additionality, BPA can stimulate other nuclear hormone receptors [4-10]; and can interfere with endocannabinoid receptors CNR1 and CNR2 [11,12]. The primary source of BPA exposure in humans is dietary, as BPA has been extensively used in food packaging since the 1960s [13]. In the United States, BPA has been detected in 93% of 2,517 urine samples collected from both adults and children [1,14,15]. BPA continuous exposure causes adverse health effects [16-28].
The primary objective of this project will be to perform a systems level analysis of the effects of environmentally relevant doses of BPA on the transcriptome and epigenome of healthy primary human cells and model the data using the adverse outcomes pathway framework with the ultimate goal of developing a human body map of BPA exposure. This will include cells derived from key body tissues where BPA elicits adverse health effects, namely prostate, gut, liver, blood, brain and testes. This will be the first in vitro study that (1) examines the effects of low dose BPA exposure jointly on the healthy human cell transcriptomes and epigenomes using a systems level approach, and (2) defines the difference between low (5 nM) and higher doses (25 nM and 100 nM) of BPA on primary cells (PrECs), and (3) specifically examines the effects of BPA on the expression of genes encoding histone and DNA methylation modifying enzymes.
All applicants must meet the academic entry requirements: https://www.qub.ac.uk/courses/postgraduate-research/biological-sciences-phd.html#entry
References
1.Kang, J.H.; Kondo, F.; Katayama, Y. Human exposure to bisphenol a. Toxicology 2006, 226, 79-89.
2.Li, Y.; Burns, K.A.; Arao, Y.; Luh, C.J.; Korach, K.S. Differential estrogenic actions of endocrine-disrupting chemicals bisphenol a, bisphenol af, and zearalenone through estrogen receptor alpha and beta in vitro. Environ Health Perspect 2012, 120, 1029-1035.
3.Matthews, J.B.; Twomey, K.; Zacharewski, T.R. In vitro and in vivo interactions of bisphenol a and its metabolite, bisphenol a glucuronide, with estrogen receptors α and β. Chemical Research in Toxicology 2001, 14, 149-157.
4.Tohme, M.; Prud’homme, S.M.; Boulahtouf, A.; Samarut, E.; Brunet, F.; Bernard, L.; Bourguet, W.; Gibert, Y.; Balaguer, P.; Laudet, V. Estrogen-related receptor gamma is an in vivo receptor of bisphenol a. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2014, 28, 3124-3133.
5.Sohoni, P.; Sumpter, J.P. Several environmental oestrogens are also anti-androgens. J Endocrinol 1998, 158, 327-339.
6.Zoeller, R.T. Environmental chemicals as thyroid hormone analogues: New studies indicate that thyroid hormone receptors are targets of industrial chemicals? Mol Cell Endocrinol 2005, 242, 10-15.
7.Bouskine, A.; Nebout, M.; Brucker-Davis, F.; Benahmed, M.; Fenichel, P. Low doses of bisphenol a promote human seminoma cell proliferation by activating pka and pkg via a membrane g-protein-coupled estrogen receptor. Environ Health Perspect 2009, 117, 1053-1058.
8.Sargis, R.M.; Johnson, D.N.; Choudhury, R.A.; Brady, M.J. Environmental endocrine disruptors promote adipogenesis in the 3t3-l1 cell line through glucocorticoid receptor activation. Obesity (Silver Spring) 2010, 18, 1283-1288.
9.Birceanu, O.; Mai, T.; Vijayan, M.M. Maternal transfer of bisphenol a impacts the ontogeny of cortisol stress response in rainbow trout. Aquatic Toxicology 2015, 168, 11-18.
10.Sui, Y.; Park, S.-H.; Helsley, R.N.; Sunkara, M.; Gonzalez, F.J.; Morris, A.J.; Zhou, C. Bisphenol a increases atherosclerosis in pregnane x receptor-humanized apoe deficient mice. Journal of the American Heart Association 2014, 3.
11.Forner-Piquer, I.; Mylonas, C.C.; Calduch-Giner, J.; Maradonna, F.; Gioacchini, G.; Allarà, M.; Piscitelli, F.; Di Marzo, V.; Pérez-Sánchez, J.; Carnevali, O. Endocrine disruptors in the diet of male sparus aurata: Modulation of the endocannabinoid system at the hepatic and central level by di-isononyl phthalate and bisphenol a. Environment International 2018, 119, 54-65.
12.Martella, A.; Silvestri, C.; Maradonna, F.; Gioacchini, G.; Allarà, M.; Radaelli, G.; Overby, D.R.; Di Marzo, V.; Carnevali, O. Bisphenol a induces fatty liver by an endocannabinoid-mediated positive feedback loop. Endocrinology 2016, 157, 1751-1763.
13.Rubin, B.S. Bisphenol a: An endocrine disruptor with widespread exposure and multiple effects. The Journal of steroid biochemistry and molecular biology 2011, 127, 27-34.
14.Schug, T.T.; Janesick, A.; Blumberg, B.; Heindel, J.J. Endocrine disrupting chemicals and disease susceptibility. J Steroid Biochem Mol Biol 2011, 127, 204-215.
15.Calafat, A.M.; Ye, X.; Wong, L.Y.; Reidy, J.A.; Needham, L.L. Exposure of the u.S. Population to bisphenol a and 4-tertiary-octylphenol: 2003–2004. Environ Health Perspect 2008, 116, 39-44.
16.Howdeshell, K.L.; Hotchkiss, A.K.; Thayer, K.A.; Vandenbergh, J.G.; vom Saal, F.S. Environmental toxins: Exposure to bisphenol a advances puberty. Nature 1999, 401, 763-764.
17.Cabaton, N.J.; Wadia, P.R.; Rubin, B.S.; Zalko, D.; Schaeberle, C.M.; Askenase, M.H.; Gadbois, J.L.; Tharp, A.P.; Whitt, G.S.; Sonnenschein, C.; Soto, A.M. Perinatal exposure to environmentally relevant levels of bisphenol a decreases fertility and fecundity in cd-1 mice. Environ Health Perspect 2011, 119, 547-552.
18.Salian, S.; Doshi, T.; Vanage, G. Neonatal exposure of male rats to bisphenol a impairs fertility and expression of sertoli cell junctional proteins in the testis. Toxicology 2009, 265, 56-67.
19.Vitku, J.; Heracek, J.; Sosvorova, L.; Hampl, R.; Chlupacova, T.; Hill, M.; Sobotka, V.; Bicikova, M.; Starka, L. Associations of bisphenol a and polychlorinated biphenyls with spermatogenesis and steroidogenesis in two biological fluids from men attending an infertility clinic. Environ Int 2016, 89-90, 166-173.
20.Manikkam, M.; Tracey, R.; Guerrero-Bosagna, C.; Skinner, M.K. Plastics derived endocrine disruptors (bpa, dehp and dbp) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS One 2013, 8, e55387.
21.Ahmed, S.; Atlas, E. Bisphenol s- and bisphenol a-induced adipogenesis of murine preadipocytes occurs through direct peroxisome proliferator-activated receptor gamma activation. International journal of obesity (2005) 2016.
22.Grun, F.; Blumberg, B. Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis. Reviews in endocrine & metabolic disorders 2007, 8, 161-171.
23.Ohlstein, J.F.; Strong, A.L.; McLachlan, J.A.; Gimble, J.M.; Burow, M.E.; Bunnell, B.A. Bisphenol a enhances adipogenic differentiation of human adipose stromal/stem cells. Journal of molecular endocrinology 2014, 53, 345-353.
24.vom Saal, F.S.; Myers, J. Bisphenol a and risk of metabolic disorders. JAMA 2008, 300, 1353-1355.
25.Doherty, L.F.; Bromer, J.G.; Zhou, Y.; Aldad, T.S.; Taylor, H.S. In utero exposure to diethylstilbestrol (des) or bisphenol-a (bpa) increases ezh2 expression in the mammary gland: An epigenetic mechanism linking endocrine disruptors to breast cancer. Hormones and Cancer 2010, 1, 146-155.
26.Prins, G.S.; Birch, L.; Tang, W.-Y.; Ho, S.-M. Developmental estrogen exposures predispose to prostate carcinogenesis with aging. Reproductive Toxicology 2007, 23, 374-382.
27.Cuomo, D.; Porreca, I.; Cobellis, G.; Tarallo, R.; Nassa, G.; Falco, G.; Nardone, A.; Rizzo, F.; Mallardo, M.; Ambrosino, C. Carcinogenic risk and bisphenol a exposure: A focus on molecular aspects in endoderm derived glands. Mol Cell Endocrinol 2017.
28.Gomez, A.L.; Delconte, M.B.; Altamirano, G.A.; Vigezzi, L.; Bosquiazzo, V.L.; Barbisan, L.F.; Ramos, J.G.; Luque, E.H.; Munoz-de-Toro, M.; Kass, L. Perinatal exposure to bisphenol a or diethylstilbestrol increases the susceptibility to develop mammary gland lesions after estrogen replacement therapy in middle-aged rats. Hormones & ca
Entrance requirements
Graduate
The minimum academic requirement for admission to a research degree programme is normally an Upper Second Class Honours degree in a relevant subject from a UK or ROI HE provider, or an equivalent qualification acceptable to the University. Further information can be obtained by contacting the School.
International Students
For information on international qualification equivalents, please check the specific information for your country.
English Language Requirements
Evidence of an IELTS* score of 6.5, with not less than 5.5 in any component, or an equivalent qualification acceptable to the University is required (*taken within the last 2 years).
International students wishing to apply to Queen’s University Belfast (and for whom English is not their first language), must be able to demonstrate their proficiency in English in order to benefit fully from their course of study or research. Non-EEA nationals must also satisfy UK Visas and Immigration (UKVI) immigration requirements for English language for visa purposes.
For more information on English Language requirements for EEA and non-EEA nationals see: www.qub.ac.uk/EnglishLanguageReqs.
If you need to improve your English language skills before you enter this degree programme, INTO Queen’s University Belfast offers a range of English language courses. These intensive and flexible courses are designed to improve your English ability for admission to this degree.
Tuition Fees
Northern Ireland (NI) 1 – £5,238
Republic of Ireland (ROI) 2 – £5,238
England, Scotland or Wales (GB) 1 – £5,238
EU Other 3 – £28,000
International – £28,000
1 EU citizens in the EU Settlement Scheme, with settled or pre-settled status, are expected to be charged the NI or GB tuition fee based on where they are ordinarily resident, however this is provisional and subject to the publication of the Northern Ireland Assembly Student Fees Regulations. Students who are ROI nationals resident in GB are expected to be charged the GB fee, however this is provisional and subject to the publication of the Northern Ireland Assembly student fees Regulations.
2 It is expected that EU students who are ROI nationals resident in ROI will be eligible for NI tuition fees. The tuition fee set out above is provisional and subject to the publication of the Northern Ireland Assembly student fees Regulations.
3 EU Other students (excludes Republic of Ireland nationals living in GB, NI or ROI) are charged tuition fees in line with international fees.
All tuition fees quoted relate to a single year of study unless stated otherwise. All fees will be subject to an annual inflationary increase, unless explicitly stated otherwise.
More information on postgraduate tuition fees.
Biological Sciences costs
Students may incur additional costs for small items of clothing and/or equipment necessary for lab or field work
Additional course costs
All Students
Depending on the programme of study, there may also be other extra costs which are not covered by tuition fees, which students will need to consider when planning their studies . Students can borrow books and access online learning resources from any Queen’s library. If students wish to purchase recommended texts, rather than borrow them from the University Library, prices per text can range from £30 to £100. Students should also budget between £30 to £100 per year for photocopying, memory sticks and printing charges. Students may wish to consider purchasing an electronic device; costs will vary depending on the specification of the model chosen. There are also additional charges for graduation ceremonies, and library fines. In undertaking a research project students may incur costs associated with transport and/or materials, and there will also be additional costs for printing and binding the thesis. There may also be individually tailored research project expenses and students should consult directly with the School for further information.
Bench fees
Some research programmes incur an additional annual charge on top of the tuition fees, often referred to as a bench fee. Bench fees are charged when a programme (or a specific project) incurs extra costs such as those involved with specialist laboratory or field work. If you are required to pay bench fees they will be detailed on your offer letter. If you have any questions about Bench Fees these should be raised with your School at the application stage. Please note that, if you are being funded you will need to ensure your sponsor is aware of and has agreed to fund these additional costs before accepting your place.
How do I fund my study?
Find PhD opportunities and funded studentships by subject area.
2.Funded Doctoral Training Programmes
We offer numerous opportunities for funded doctoral study in a world-class research environment. Our centres and partnerships, aim to seek out and nurture outstanding postgraduate research students, and provide targeted training and skills development.
The Government offers doctoral loans of up to £26,445 for PhDs and equivalent postgraduate research programmes for English- or Welsh-resident UK and EU students.
Information on Postgraduate Research scholarships for international students.
How to Apply
Apply using our online Postgraduate Applications Portal and follow the step-by-step instructions on how to apply.
Find a supervisor
If you’re interested in a particular project, we suggest you contact the relevant academic before you apply, to introduce yourself and ask questions.
To find a potential supervisor aligned with your area of interest, or if you are unsure of who to contact, look through the staff profiles linked here.
You might be asked to provide a short outline of your proposal to help us identify potential supervisors.
Submit an application that gets noticed.
Don't let a weak CV or cover letter cost you the offer. Get expert help tailoring your application to this exact lab: CV, SOP, cover letter & interview prep.
Boost my application →Want fewer missed deadlines?
Pick WhatsApp or Telegram, then follow a channel (Graduate → Post-PhD).