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BB20023/BB20110 DNA & disease (cancer biology) Dr. Momna Hejmadi [email protected] https://moodle.bath.ac.uk/moodle5/login/index.php How to access learning materials: Go to the URL above and click Yes to both security alert and display questions. LOGIN with your BUCS username & password. Click on the DNA and disease course listed to access all learning materials related to this unit. Any problems? Email me at [email protected] (FIRST please ensure that you are registered to do the unit with Teresa Buckley [email protected]) How is this unit assessed? Part of the lecture content (DNA replication, damage and repair mechanisms) is incorporated as part of an interactive teaching resource that is available at the following URL https://moodle.bath.ac.uk/moodle5/login/index.php . This tutorial is designed to help you understand and learn some of the fundamental mechanisms of DNA replication, damage and repair at your own pace based ONLY on and time. It is meant to be an overview of the whole process and you online tutorial on could then read up texts / reviews to get in depth information. DNA replication, There will be 2 workshop sessions per degree cohort (E.g. damage and repair biochemistry, MCB etc) which is aimed at supporting the content of mechanisms (contents the tutorial. You are strongly encouraged to go over the tutorial of the tutorial PRIOR to attending the workshop, to enable you to fully participate handout). and benefit from these sessions. A written report on a single laboratory practical on DNA repair will comprise 20% of the unit marks. In order to do this practical, you have to do 2 things Practical report 1) Try the animation of experiment 1 of the practical, which has been designed to understand the process 2) Complete the pre-practical quiz online (see this Moodle site for details) 1 hr examination on the lecture topics (lectures 9-21 ) ONLY. This will Exam essay be held on the ‘unit assessment days’ in Jan 2007 (Example paper below) Multiple Choice Questions (MCQ) 20% 20% 60% General Reading List • The biology of Cancer by Robert Weinberg (Garland Publishers ) Other useful books to consult • Cancer Biology (2000; 2nd ed) by RJB King (Prentice Hall Publishers) • DNA repair and mutagenesis (2002) by Friedberg EC, Walker g and Siede W • Plus reviews / articles All lectures by MVH in 3WN 2.1 Dates 1 4/10 6/10 2 11/10 13/10 3 18/10 20/10 4 25/10 27/10 5 1/11 3/11 6 8/11 10/11 7 15/11 17/11 8 22/11 24/11 9 29/11 1/12 10 6/12 8/12 tbc 11 13/12 15/12 Time 11.15 12.15 11.15 12.15 11.15 12.15 11.15 12.15 11.15 12.15 11.15 12.15 11.15 12.15 11.15 12.15 11.15 12.15 11.15 12.15 tbc 11.15 12.15 TOPICS Introduction: nature of cancer DNA replication Biochem Workshop 1 DNA damage and repair Biochem Workshop 2 DNA replication MCB/NS/other Workshop 1 DNA damage and repair MCB/NS/other Workshop 2 DNA replication Biology Workshop1 DNA damage and repair Biology Workshop 2 Revision session on above Oncogenic viruses No lecture Apoptosis video MCQ test (VENUE 3WN 2.1 and 3WN 3.8) No lecture (No Room Available!) Oncogenes & tumour suppressor genes 1 Oncogenes & tumour suppressor genes 2 Oncogenes & tumour suppressor genes 3 Apoptosis Angiogenesis and metastasis Cancer therapy 1 - conventional Cancer therapy 2 – Angiotherapy Lab report assessment Cancer therapy 3: Immunotherapy Cancer therapy 4 – gene therapy Cancers are clonal descendents of one cell Cancer arises by successive mutations in a clone of proliferating cells Cancer phenotype results from accumulation of mutations in the clonal progeny of cells • Clone of cells overgrows due to accumulation of mutations controlling proliferation. • Disseminates through bloodstream to other parts of body • Forms tumor Introduction: The 6 Superpowers Introduction: The 6 Superpowers Cancer Cell Normal Cell 1 GO STOP SLOW 1. Most cells wait for a ‘Go signal before dividing. Cancer cells don’t bother waiting… they produce their own ‘Go’ chemical messages and continue dividing. Introduction: The 6 Superpowers Cancer Cell Normal Cell 1 GO 2 STOP SLOW 2. Even if the neighbouring cells produce a ‘Stop’ signal, cancer cells override these signals and continue dividing. Introduction: The 6 Superpowers Cancer Cell Normal Cell 1 GO 2 STOP Apoptosis 3 SLOW 3. Normal cells sometimes react to stress by triggering a ‘Self Destruct’ button and killing itself, but cancer cells sneak past these self destruct signals and continue to divide, thus accumulating more mutations. Introduction: The 6 Superpowers Cancer Cell Normal Cell 1 GO 2 STOP Apoptosis 3 SLOW 4 Food Supply 4. Cancer cells make sure they can keep dividing by stimulating the growth of new blood vessels to keep their nutrient supply lines open. Introduction: The 6 Superpowers Cancer Cell Normal Cell 1 GO 2 STOP Apoptosis 3 SLOW 4 Food Supply 5 Immortality 5. One of the key superpowers is immortality. Unlike normal cells which have a finite life span, cancer cells manipulate their own DNA (via repetitive DNA sequences called telomeres) to keep dividing for a lot longer. Introduction: The 6 Superpowers Cancer Cell Normal Cell 1 GO 2 STOP Apoptosis 3 SLOW 4 Food Supply 5 Immortality 6 Metastasis 6. Most tumours that show these traits are trouble, but the lethal nature of cancer is due to its ability to spread to other location or metastasize. 90% of cancer deaths are due to metastasis. General cancer phenotype includes many types of cellular abnormalities Changes that produce genomic and karyotypic instability • Defects in DNA replication machinery – lost capability to reproduce genome faithfully • Increase rate of chromosomal aberrations – fidelity of chromosome reproduction greatly diminished Changes produce genomic and karyotypic instability and often show gross rearrangements Normal cells Cancerous cells Changes that produce a potential for immortality • Loss of limitations on the number of cell divisions • Ability to grow in culture – normal cells do not grow well in culture • Restoration of telomerase activity Changes that enable tumor to disrupt local tissue and invade distant tissues • Ability to metastasize • Angiogenesis – secrete substances that cause blood vessels to grow toward tumor • Evasion of immune surveillance Some cancers run in families such as retinoblastoma Most cancers result from exposures to mutagens • If one sibling or twin gets cancer, other usually does not • Populations that migrate – profile of cancer becomes more like people indigenous to new location Most cancers result from aging Tumours as complex tissues Reading – any one of … www.els.net