PhD position in biostatistical/molecular epidemiology of cancer / translational cancer research

The UCD School of Biomolecular & Biomedical Science, University College Dublin, Ireland, is pleased to announce this funded PhD studentship which will be supervised by a recently appointed Ad Astra Fellow. Students will be enrolled onto UCD’s structured PhD programme which includes some taught elements and transferrable skills training providing an excellent foundation for a research career. https://www.ucd.ie/graduatestudies/researchprogrammes/structuredphd/

The studentships are open to EU and non-EU candidates and are for a maximum of four years, renewable each year, subject to satisfactory progress.

Project Title: 

Exploring the role of microbiota and metabolic interactions in the development of liver and pancreatic cancers

Studentship details: Stipend of €18,000/year (plus tuition fees) for 4 years

Start date: September 2020

Supervisor Details: Dr David Hughes, UCD School of Biomolecular & Biomedical Science, University College Dublin, Ireland.https://people.ucd.ie/david.hughes

About the Project

Disturbances to the normal gut microbiota flora (dysbiosis) and resultant alterations in microbial products are increasingly implicated in cancer development [1]. While most of these studies have focused on colorectal cancer, there is emerging evidence of a link between microbiome dysbiosis and altered metabolism in the development of cancers at various sites in the gastrointestinal tract, including liver (beyond hepatitis) and pancreatic cancers, which form the focus of this PhD project [2-4]. However, epidemiological evidence, especially from prospective cohorts, is sparse. Recent data on gut barrier function in liver cancer from our project collaborators indicates that leakage of bacterial toxins and bacterial translocation from the gut via the portal vein exposes the liver to a high inflammatory environment, leading to cancer development [5,6]. Furthermore, although most studies on the microbial dysbiosis in cancer have focused on bacterial species, recent reports suggest an appreciable influence of the fungal mycobiome in development of gastrointestinal cancers such as colorectal cancer [7] and pancreatic cancer [8].

The main aims of this project will be to analyse interactions between microbiome sequence data (tissue analyses) and antibodies to bacterial species (blood screening), metabolites such as bile acids and short chain fatty acids (human and microbiota-derived), and markers of gut barrier function, to assess their contribution to the risk of microbial-mediated gastrointestinal cancer development. A secondary aim will be to study the interactions with host genetics and nutritional factors as potential mediators of microbiota disease pathogenesis. The project will highlight the importance of the interaction between microbial infection, dysbiosis (including bacterial, viral, and fungal), gut barrier function, and metabolism in the aetiology of hepatobiliary and pancreatic cancers.

 

Position summary

The PhD project will benefit from a collection of European human cohort studies, including case-control and  nested case control studies of hepatocellular carcinoma (the main type of liver cancer) and other cancers of the hepatobiliary tract (together termed hepatobiliary cancers) and pancreatic cancers to analyse metagenomic sequences, antigen serology data, metabolite data, and markers of gut barrier function to test the hypothesis of a major contribution from microbial dysbiosis and metabolic dysfunction to gastrointestinal cancer aetiology.

This PhD will involve both laboratory assays such as ELISA assays, qPCR, metagenomic sequencing, mass spectrometry, but there will be a major focus on biostatistical and bioinformatic approaches. These analytical methods will be used to examine modification of microbial associations by gut permeability and microbial and human metabolites, nutrient levels, host genetic variation and other dietary/lifestyle factors.

The project will add to our existing data on hepatitis infection status and a host of other biomarker data on the hepatobiliary cancer cases and controls from a prospective cohort, including targeted and untargeted metabolomics and Metabolic Syndrome Score assessments. These analyses will be combined with metagenomic data and human host genetic data (e.g., immune gene variants, bile acid receptors gene variants, etc) that are available in data repositories. This project will be nested within a larger ongoing examination of the aetiology of gastrointestinal cancers related to the same factors.

Ethical Approval: Informed consent was obtained from all participating subjects for these studies in accord with the Helsinki declaration. All samples are coded to protect patient anonymity. The design of the study was approved by the Ethical Committee of the collaborating academic centres and hospitals.

 

Principal Duties and Responsibilities

Candidate criteria

The successful candidate should have interests in biostatistical and bioinformatic techniques, and microbial, nutrition, and genetics/genomics research in cancer. Preferred fields of study and training include Biostatistics, Bioinformatics, Epidemiology, Microbiology, Nutrition, and Genetics. A knowledge and / or enthusiasm for bioinformatic and statistical analysis of molecular data  (such as blood serotyping, genetic variation analyses, next generation metagenomic sequencing, and metabolomics) is essential.  The candidate must either have experience of, or be willing, to learn biostatistical and bioinformatic methodologies for the analyses required in this project.

Applicant Requirements

Applicants must have, or expect to have, reached a minimum of an upper second-class (2.1) degree or equivalent in a relevant honours Bachelor’s or Master’s degree. Excellent written and oral communication skills and a high level of competence in the English language are essential.

http://www.ucd.ie/registry/admissions/elr.html

Mandatory:

  • A BSc (2.1 hons or higher) in Statistics, Bioinformatics, Mathematics, Microbiology, Biology, Genetics, Nutrition, Biochemistry, Biotechnology, Biomedical Science, Immunology, Public Health, Epidemiology
  • Basic biostatistical analysis methodologies
  • Good verbal communication & writing skills

 

Desirable:

  • Experience in Next Generation Sequencing based assays
  • Experience in metagenomic and/or genomic sequence analysis
  • Experience in Metabolomics and/or Mass spectrometry
  • Experience in data handling
  • Understanding and experience of database management and conducting data analysis using

statistical software, e.g. SPSS, Stata, SAS, R, MATLAB

  • Experience in reviewing literature
  • Excellent organisational skills

 

Applicants should submit the following to the supervisor of this project (to david.hughes@ucd.ie) as a single .pdf document:

1. A cover letter outlining their interest in the project and any relevant experience

2. A detailed CV (including a list of any publications if applicable)

3. The names and contact details of two academic referees

Interviews will take place via video call in July.

CLOSING DATE: SUNDAY 12th JULY, 2020.

 

Funding Notes

The studentship award includes full tuition fee waiver, a PhD stipend of €18,000 per annum, and a research budget to cover research costs associated with the project.

 

Skills & techniques that the student will learn from the project

This project is designed to provide a graduate with the knowledge and practical skills to pursue a career in biostatistical / molecular epidemiology of cancer and/or translational cancer research. The foundations of UCD principles, good research practise and ethics, professionalism, good laboratory practice, science communication (presentation skills and science writing), and the importance of validation and statistical evaluation of results will be highlighted. During this PhD project the student will be helped to develop skills needed for inter-disciplinary collaboration as well as the ability to work independently.

The student will become familiar with the following techniques: metagenomic sequencing (i.e., next generation sequencing of the microbiome), Mass spectrometry analyses for metabolomics, ELISA assays, qPCR, statistical methodologies for large cohort studies and basic bioinformatics, extraction of genetic data from microbiota metagenomic and human GWAS studies, cancer epidemiology methodology and study design, cohort study analysis, logistic regression methods, proportional hazards models, and mediation analysis to investigate the role of metabolic dysfunction,  inflammation, and nutrient status as mediators in the cancer and microbiome association. Comprehensive analysis suites (e.g., SparCC, QIIME, HUMAnN and MG-RAST) will be used to assess metagenomic sequence reads and metatranscriptomic gene expression levels. For example, bioinformatic modelling methods will be used to assess possible mechanisms of mycobiome associated cancer development and clinical outcomes, such as target fungal invasion, disturbances to gut flora eubiosis [7], potential oncogenic effects on the complement system via mannose-binding lectin [8], and selenium status (considered potentially protective viral and fungal infection or from their mutation into more virulent strains [9]).

 

This research project is at the interface of biostatistics, microbial & metabolic cancer epidemiology, and the analysis of exposure/environmental factors. The project and the student will benefit markedly from the input of eminent collaborators and their institutional supports in the International Agency for Research on Cancer (IARC) in Lyon, France, the German Cancer Centre (DKFZ) in Heidelberg, the University of Copenhagen, Denmark, the Rollins School of Public Health (RSPH) at Emory University in Atlanta, USA, and Charles University, Prague, Czech Republic. These institutes rank among the leading cancer epidemiology and translational cancer research centres worldwide. Exchange working visits will be encouraged between these institutes and UCD.

 

The project will have access to the largest prospective cancer & nutrition cohort in the world (the European Prospective Investigation of Cancer and Nutrition cohort), and patient cohort studies from Ireland and the Czech Republic. The student will be provided the opportunity to present their work at important relevant national and international conferences.

 

Which undergraduate disciplines are relevant for this project

Statistics, Bioinformatics, Mathematics, Epidemiology, Biology, Microbiology, Genetics, Biochemistry, Biotechnology, Biomedical Science, Pharmacology, Immunology, Public Health.

 

References

  1. Scott AJ, Alexander JL, Merrifield CA, Cunningham D, Jobin C, Brown R, Alverdy J, O'Keefe SJ, Gaskins HR, Teare J, Yu J, Hughes DJ, Verstraelen H, Burton J, O'Toole PW, Rosenberg DW, Marchesi JR, Kinross JM. The International Cancer Microbiome Consortium Consensus Statement on the Role of the Human Microbiome in Carcinogenesis. Gut 2019 Sep;68(9):1624-1632. PMID: 31092590.
  2. Elsalem L, Jum'ah AA, Alfaqih MA, Aloudat O. The Bacterial Microbiota of Gastrointestinal Cancers: Role in Cancer Pathogenesis and Therapeutic Perspectives. Clin Exp Gastroenterol. 2020 May 6;13:151-185.
  3. Jia W, Xie G, Jia W. Bile acid–microbiota cross-talk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol. 2018 Feb; 15(2): 111–128. PMID: 29018272
  4. Piñero F, Vazquez M, Baré P, et al. A different gut microbiome linked to inflammation found in cirrhotic patients with and without hepatocellular carcinoma. Ann Hepatol. 2019;18(3):480‐ doi:10.1016/j.aohep.2018.10.003.
  5. Yang B, Petrick JL, Thistle JE, et al. Bacterial Translocation and Risk of Liver Cancer in a Finnish Cohort. Cancer Epidemiol Biomarkers Prev. 2019;28(4):807‐
  6. Fedirko V, et al, and Jenab M. Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study. BMC Med. 2017;15(1):72.
  7. Coker OO, Nakatsu G, Dai RZ, Wu WKK, Wong SH, Ng SC, Chan FKL, Sung JJY, Jun Yu. Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer. Gut 2018;0:1–9.