Gene-environment interactions: Genetics and Molecular Biology

1. BSc in Medical Sciences with Gastroenterology & HepatologyCourse Leaders:Prof Julian Walters, Dr Shahid Khan, Prof Simon Taylor-Robinson, Dr Belinda Smith, Dr Marco Purbhoo, Dr Horace Williams, Dr Lakshmana Ayaru, Dr Harry Antoniades,Olive Thomas (administrator)

2. Introductory course:Gastroenterology & Hepatology: an introductionCourse structure and introductionCore skills: Statistics, references, critical appraisalBasic molecular biology, immunologyReview of common pathology in liver and gutRelevance to clinical presentationsProf Julian WaltersDr Marco Purbhoo(St Mary’s and Hammersmith)

3. Module 1:Gene-environment interactions: Metabolic, Genetic & Nutritional disorders of gut & liverModule leaders: Prof Julian Walters Dr Horace Williams(Hammersmith)

4. Gene-environment interactions: Genetics and Molecular Biology Aa AA AA Aa AA Aa

5. Gene-environment interactions: Inflammatory Bowel Diseases Luminal Bacteria NOD2/CARD15 TNF-α NO PAF MMP IL-18IL-16 IL-1βIL-6TNF-α IL-15 TNF-αIFN-γ IL-12 TGF-β1IL-10 IL-23IL-7 Terminal Ileum Colon Multiple genes involved

6. Gene-environmentinteractions: Coeliac Disease Gluten Villous atrophy HLA-DQ genes and others

7. Gene-environment interactions: Haemochromatosis Excess Iron Causes Widespread Pathology: • Liver • cirrhosis • hepatocellular carcinoma • Regulation of intestinal iron absorption • HFE and other mutants

8. Gene-environment interactions Nutrition & metabolism Malnutrition, absorption, nutrition support Food choices, appetite control, obesity & related diseases

9. Module 2:Diagnostic & therapeutic principles in GI & liver disease: emphasis on the science underlying imaging, and on neoplasiaof Simon Taylor-Robinson (Hammersmith)Module leaders: Dr Belinda Smith Dr Shahid Khan Dr Laksh Ayaru(St Mary’s & Hammersmith)

10. Diagnostic & therapeutic principlesScientific principles & use of CT, US, MRI, angiography etc.

11. Diagnostic & therapeutic principlesNew modalities in diagnosis & therapy Endoscopic therapy, EUS, MRCP

12. Diagnostic & therapeutic principlesEpidemiology ofCancers in the GI Tract

13. Diagnostic & therapeutic principlesColorectal neoplasia

14. Module 3:Infective, immunological & inflammatory mechanisms in gut & liver diseaseModule leaders: Dr Marco PurbhooDr Harry Antoniades(St Mary’s)

15. Infective, immunological & inflammatory mechanisms HBV Infection

16. Infective, immunological & inflammatory mechanisms Helicobacter pylori & Duodenal Ulcers

17. Infective, immunological & inflammatory mechanismsClinical characteristics of acute Graft Versus Host Disease First 100 days post-transplant Severe GVHD affects 10-30% of patients

18. Part C: ProjectsorAdditional taught courses

19. Lab-based Projects Hepatitis C virus NS4B-roles in extra-hepatic replication and modulating IRES function Undigested plasmid DNA Insert

20. Clinical projects Trends in mortality & incidence rates for intrahepatic cholangiocarcinoma & selected hepatobiliary tumours

21. Lab based projects with a clinical component RP1 site Homozygous TT (wild-type) Heterozygous CT  Homozygous CC Polymorphisms in FABP6 gene promoter in bile acid malabsorption

22. Clinical projects with a lab component Cerebral 1H Spectroscopy in Hepatitis C patients with cognitive dysfunction

23. BSc Projects 2013-4 (1) • Circulating Bacterial DNA in patients with acute-on-chronic liver failure: a cause of sepsis and early mortality (laboratory) • "T cells in human acute liver failure: phenotypic and functional properties (Laboratory)" • Secretory Leukocyte Protease Inhibitor (SLPI) and IL-10: possible key players in the altered immune functions of monocytes in human acute liver failure (lab) • Defining healthy and unhealthy patterns of gut bacteria. (laboratory project) • Identification of a novel anti-apoptotic gene in HCC (Laboratory) • Aetiological factors of hepatocellular carcinoma in West Africans (Clinical) • Does Right rather than Left lateral starting position lead to quicker completion of Colonoscopy? ( (Clinical) • Metabolic differences in the pathogenesis of HCC by aetiological factors (Laboratory) • Enzymatic analysis of fecal water (laboratory) • Assessment of HBsAgseroprevalence among blood donors in Gambia (RVTH) and attendance rate to liver clinic (laboratory) • Serum HBsAg titres in a treatment-naive Gambian cohort of HBV-infected patients (laboratory) • Malaria Hepatitis B coinfection in Gambia (laboratory) • Identification of innate immune effector molecules active against hepatitis B virus: Literature review (Library) • Regulation of Lectin-Like Transcript 1 (LLT1) expression on Hepatocytes by Danger signals (Laboratory) • Outcomes from treating bile acid malabsorption (Clinical) • Identification of innate immune effector molecules active against hepatitis B virus(Laboratory) • Systematic Review on Environmental Enteric Dysfunction (Library)

24. BSc Projects 2013-4 (2) • Comparison of non-invasive assessments of fibrosis in NAFLD patients (Clinical) • Urinary metabolic profiling by ultra-performance liquid chromatography mass spectrometry to stratify complications of cirrhosis (Laboratory) • Stem cell biology and colorectal carcinogenesis (laboratory) • Genetic risk factors for Colorectal Cancer (Literature review) • The clinical utility of microvasculature assessment of the liver in focal liver lesion and diffuse liver disease characterisation (Clinical) • Effects of novel bile acid analogues on ileal gene expression (Laboratory) • Faecal calprotectin in bile acid diarrhoea (Laboratory) • Vitamin deficiencies in patients treated with bile acid sequestrants.(Laboratory) • fMRI and diffusion tensor imaging in hepatic encephalopathy (Laboratory) • Virology of hepatitis C (Laboratory) • Audit of hepatocellular cancer screening at St Mary's Hospital (Clinical) • Audit of liver transplanatation assessments at Imperial NHS Trust (Clinical) • Health service utilisation in HIV/hepatitis coinfection cirrhosis v non-cirrhotic (Clinical) • Clinical outcomes of fibroscanned-patients at St Mary's Hospital (Clinical) • Clinical project on anti TNF drug levels with a new cell based assay (Clinical) • Metabonomics Study of urine in a UK normal volunteer cohort and in patients with bile duct cancer (Laboratory) • Treatment outcomes in HIV/hepatitis B coinfection (Clinical) • Definition of the phenotype of Polymerase Proofreading-Associated Polyposis (Laboratory)

25. BSc in Medical Sciences with Gastroenterology & Hepatology • Why? • Interesting and different range of pathological situations • Many different underlying scientific processes: • Genetic, nutritional, immunological, infective, inflammatory, neoplastic, epidemiology • Efficient and popular course.