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A human body map of bisphenol-A (BPA) exposure: Systems level analysis of genomic and epigenomic alterations in primary human cells

School of Biological Sciences | PHD
Funding
Unfunded
Reference Number
SBIO-2020-1060
Application Deadline
None specified
Start Date
None specified

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

Project Summary
Supervisor
Professor Gary Hardiman
Mode of Study

Full-time: 3 years


Apply now Register your interest

Biological Sciences overview

The School of Biological Sciences provides PhD and MPhil (research degree) programmes in subjects ranging from basic biochemistry, molecular genetics and cancer research, to agricultural science, marine ecology and the economic evaluation of ecosystem services and food retailing. If you have a topic or research question in mind, please use the Find a Supervisor link (see Apply tab) to identify the most appropriate member of staff to support your idea. If not, don't worry, we regularly advertise funded projects and there is no harm in browsing our academic staff profiles for inspiration and then contacting whoever seems best: we are very open to applications from suitably qualified people interested in scientific research. In every case, a PhD or MPhil course provides the means of being part of a cutting edge scientific research team and contributing to genuine new discoveries or the development of new methods for practical use. If you cannot study full time, we offer pro-rata part time research degree programmes as well.

To help orientation, the School is organised into three research theme clusters:

- Ecosystem Biology and Sustainability
- Microbes and Pathogen Biology
- Food Safety and Nutrition

Ecosystem Biology and Sustainability:

In this cluster, you could research biodiversity and ecosystem services for environments ranging from tropical forests to deep oceans, using field techniques and skills such as wildlife tracking, taxonomy, geostatistics, molecular and genetic ecology, foodweb-analysis, microcosm and mesocosm experiments and mathematical/computational methods. Alternatively, you could study the behaviour and temperament of wild, agricultural or domestic animals and their implications for welfare and ability to respond to environmental change. Potential research projects include phylogenetic analysis of rare and newly discovered species, examination of ecological interactions in tropical systems, agricultural soils, or marine communities, using state-of-the-art genetic analysis, surveys using drones or satellite tagging, or experiments in tanks and field plots, including careful and ethical examinations of animal behaviour. Projects range from theoretical analysis of stability in ecosystems, through discovery of new species and mechanisms of interaction, or responses to climate change, to the assessment of EU agri-environment schemes, development of new methods for commercial fisheries management and economic evaluations of conservation measures. Projects very often have an international dimension and include collaboration with other researchers worldwide.

Microbes and Pathogen Biology:

This cluster covers a diverse array of research interests united by an emphasis on molecular approaches applied to both fundamental and applied questions over the range from molecular to ecological systems. These interests include biochemistry, food safety, microbiology and parasite control with applications in human and animal health, nutrition, plant and soil sciences, and agricultural development. We have a long-standing reputation in parasite biology and in applied microbiology (for example in clearing land of contamination) as well as strong contributions to fundamental methods in understanding cancer, developing veterinary vaccines and molecular detectors for toxins and diseases. The common thread is our strong molecular approach using and developing cutting edge genomic, transcriptomic/proteomic methods. Research students in this cluster enjoy a range of strong international links across Europe, Asia, North and South America.

Food Safety and Nutrition:

Research opportunities offered by this cluster span the entire food chain "from farm to fork" with a strong emphasis on food safety and nutrition, public health and food security. In this cluster you would conduct research under the supervision of leading scientists based in the Institute for Global Food Security and benefit from integration with business experts, helping you gain leadership positions nationally and internationally.

Biological Sciences Highlights
Industry Links
  • The School has a wide range of strong, international links with governments, academia and industry, into which postgraduate research students are integrated.
World Class Facilities
  • Students will have the full use of modern, world-class laboratories, equipped with state-of-the-art, highly advanced analytical instruments and facilitated by world-class field work provision.
  • Students studying in the Food Safety and Nutrition programme will gain excellent practical experience of advanced technology and bioanalytical techniques for food safety analysis and monitoring, including: 1. GC, HPLC and UPLC separation platforms; 2. ICP, IR, qToF and QqQ mass spectrometers; 3. Microbiological research facilities; 4. Antibody production and biomolecule binder development; 5. Cell culture suite and bioanalytical assay detection systems; 6. NMR, NIR and Raman spectrometers; 7. Proteomic and metabolomic profiling tools RT-PCR; 8. Transcriptomic profiling; 9. Next-generation sequencing; 10. Multiplex biosensor platforms and LFD development.
Key Facts

  • Over 80% of science jobs are in areas of Biological Sciences.
  • Most of the critical problems facing humanity - disease, climate change and food security - require biological understanding to solve them.
Brexit Advice

Information on the implications of Brexit for prospective students.

Course content

Research Information

PhD Supervisors
Information on the research interests and activities of academics in Biological Sciences can be accessed via the School website and the Find a Supervisor facility (see Apply tab).

Career Prospects

Introduction
Queen's postgraduates reap exceptional benefits. Unique initiatives, such as Degree Plus and Researcher Plus bolster our commitment to employability, while innovative leadership and executive programmes alongside sterling integration with business experts helps our students gain key leadership positions both nationally and internationally.

Employment after the Course
Graduates have gone on to be professional research scientists, consultants, or hold technical and junior executive positions in commerce and government.

People teaching you

Dr Keith Farnsworth
Chair of School Postgraduate Research Committee
School of Biological Sciences
For a PhD you will have a principal and second supervisor who advise your independent studies and will be supported by a wider team from the academic staff - who they are, of course, depends on your project. For further details on any aspect of postgraduate research degrees within the School of Biological Sciences, contact: biosciences-pg@qub.ac.uk.

Learning Outcomes

A research degree offers students an opportunity to foster their capacity for independent research and critical thought. It also allows students to explore an area of interest and so understand and solve theoretical and practical problems within the field. Undertaking a research degree can enhance a student’s written and oral communication skills and a PhD is almost always a formal requirement for an academic post.

Course structure

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Assessment

Assessment processes for the Research Degree differ from taught degrees. Students will be expected to present drafts of their work at regular intervals to their supervisor who will provide written and oral feedback; a formal assessment process takes place annually.

This Annual Progress Review requires students to present their work in writing and orally to a panel of academics from within the School. Successful completion of this process will allow students to register for the next academic year.

The final assessment of the doctoral degree is both oral and written. Students will submit their thesis to an internal and external examining team who will review the written thesis before inviting the student to orally defend their work at a Viva Voce.

Feedback

Supervisors will offer feedback on draft work at regular intervals throughout the period of registration on the degree.

Facilities
Full-time research students will have access to a shared office space and access to a desk with personal computer and internet access.

Entrance requirements

Graduate
The minimum academic requirement for admission to a research degree programme is normally an Upper Second Class Honours degree 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.

As a result of the COVID-19 pandemic, we will be offering Academic English and Pre-sessional courses online only from June to September 2020.

  • Academic English: an intensive English language and study skills course for successful university study at degree level
  • Pre-sessional English: a short intensive academic English course for students starting a degree programme at Queen's University Belfast and who need to improve their English.

Tuition Fees

Northern Ireland (NI) £4,407
England, Scotland or Wales (GB) £4,407
Other (non-UK) EU £4,407
International £21,300

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.

How do I fund my study?
1.PhD Opportunities

Find PhD opportunities and funded studentships by subject area.

2.Doctoral Training Centres at Queen's

Queen's has eight outstanding competitive Doctoral Training Centres, with each one providing funding for a number of PhD positions and most importantly a hub for carrying out world class research in key disciplines.

3.PhD loans

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, £10,000 for students in Scotland and up to £5,500 for Northern Ireland students.

4.International Scholarships

Information on Postgraduate Research scholarships for international students.

Funding and Scholarships

The Funding & Scholarship Finder helps prospective and current students find funding to help cover costs towards a whole range of study related expenses.

How to Apply

Apply using our online Postgraduate Applications Portal go.qub.ac.uk/pgapply 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.