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Dr Chris Willmott Dept of Biochemistry University of Leicester [email_address] Putting bioscience into context: exercises to enhance engagement Society for Experimental Biology (Canterbury) University  of Leicester
Outline of session  ‘ Problem-based learning’ in Biology “ How does my course content relate to the    outside world?” Examples – some mine, some others University  of Leicester
Outline of session  Case studies/ scenarios Debate and role-play Card-based problems  TV programmes, inc. Structured activity based on news footage  Clips from other programmes Knowing what’s on and when University  of Leicester
Case Study (1) - Carl J.  At age 5, viral myocarditis   (inflammation of heart muscle) Developed prolonged and   worsening heart difficulties   (dilated cardiomyopathy) Now aged 12, Carl easily   becomes tired and is frequently   breathless; he cannot walk far A heart transplant is his only   hope of survival No human donor has become   available, but there is a trial   programme using pig hearts Would YOU advise Carl’s parents to put him forward for the trial?  Why/why not? University  of Leicester
Case Study (1) - Carl J.  Example comments include: “ He’s going to die anyway, so why not give it a try” “ Yuk!” “ What about animal rights?” These comments are brought into discussion at relevant point in subsequent discussion e.g. risk of viral infection means more than just safety of individual patient at stake University  of Leicester
Case study (2) – Wendy & Paul  Wendy and Paul Carter have been married for twelve years.  They would love to have children.  Unfortunately, Wendy had breast cancer when she was 28 and although the chemotherapy has brought total remission from the disease it also caused damage to her ovaries that have made her infertile. Paul and Wendy have been on the waiting list at their local IVF clinic for a number of months awaiting donated eggs to try and have a baby.  At present, however, there are 200 potential mothers seeking each donated egg and the couple know that realistically they may never receive a donated egg via the normal channels. Researchers at the hospital attached to the IVF clinic have recently gained permission to carry out experimental procedures using eggs harvested from aborted foetuses.  The technique is controversial, but for Paul and Wendy it may represent their only chance to receive a donated egg. University  of Leicester
What are the issues involved in this case? -  Feel free to include aspects of the case that are likely to be issues for other people, your contributions need not be limited to your own opinions. Case study (2) – Wendy & Paul  University  of Leicester
This case  - content is fictional but based on real ideas    and statistics - used in Session 1 of 6 in bioethics series - used as vehicle to introduce more   philosophical aspects Case study (2) – Wendy & Paul  University  of Leicester
Deontological (first principles) Does a foetus have any rights? Does the “mother” have any rights or say in the  upbringing of their “grandchild”? Should people be allowed to manipulate nature for their own gain? Consequentialist (outcomes) What would be the psychological effects on the   child? If the child turns out to be “defective” then who is culpable?  What is the likelihood of success? Case study (2) – example comments  University  of Leicester
Pharmaceutical development (1)  Concerned by news coverage of increasing MRSA infection rates, you and your fellow directors of SmartaPharma plc decide to develop a new antibacterial compound.  What stages will you need to go through from your initial idea until you have an effective (and profitable) medicine available for patients?   University  of Leicester
Pharmaceutical development (2)  Scientific stages in drug development: - finding lead compound -  in vitro  testing - animal testing - clinical trials: stages  - who?  - how many? - how long? - why done? Image from http://www.sandc.com University  of Leicester
Pharmaceutical development (3)  Economic and legal stages:  - students always forget to file a patent! - permission to administer:  - when?  - who from? - marketing Image from http://www.foremostmachine.com University  of Leicester
Pharmaceutical development (4)  Lead into discussion of: - drug lifetime - named v generics - patent extending - counterfeiting - why are drug companies actually moving    AWAY from antibacterials? Image from http://industry.am.nsk.com University  of Leicester
Debate & role-play  Traditional debate, “This house believes…” Role-play allows students to become more immersed   in the scenario Example – Use of the rainforest (Southgate, 2002) University  of Leicester
Use of the rainforest  UN Conference on Environment and Development Roles, representatives of: - Government in country - A logging company - Indigenous forest-dwellers - Subsistence farmers in the area - Cattle ranchers - A multinational chemical company - UN commission on Sustainable Development Southgate (2002) University  of Leicester
Other suitable role-play scenarios  Pre-implantation Genetic Diagnosis - “Saviour sibling” Roles, e.g.:  - specialist doctor - sick child - parents - genetic counsellor  - pro-life campaigner Task set, might be: Write scientifically accurate sketch (as team), or   Research role ready for improvised TV show University  of Leicester
© Annette Cashmore, GENIE CETL, University of Leicester Card-based problems (1)  Production of Medically Important Proteins Using Recombinant DNA Techniques
8 © Annette Cashmore, GENIE CETL, University of Leicester Card-based problems (2)  FLOW DIAGRAM OF CLONING A GENE You must now decide how to clone your gene : (1) cDNA library - Go to 9 (2) genomic library - Go to 10
36 © Annette Cashmore, GENIE CETL, University of Leicester Card-based problems (3)  YEAST VECTORS YEp213 Multicopy, DNA plasmid Shuttle vector - bacterial and yeast origins of replication (ORI) 2µm sequences (ORI andSTB) Selective markers : Yeast : auxotrophic marker -  LEU2  gene (LEU2) Bacteria : Ampicillin resistance (Amp R)   Tetracycline resistance (Tet R) Cloning vector Go to 37
YEAST-SUMMARY You have cloned your gene into a yeast expression vector.  Check the table to see if you have expressed a protein. 76 © Annette Cashmore, GENIE CETL, University of Leicester Card-based problems (4)  78 yes Somatostatin genomic Hind III pJP31 78 yes Factor IX 78 yes hEGF 78 yes Somatostatin cDNA Hind III pJP31 81 no Any cDNA / genomic Bam HI YEp213 Go to Expression  Protein Insert DNA Enzyme site Plasmid
81 FAILURE !!!!! You have not been able to express your gene  in this host - vector system.  The reasons for this are : You have cloned into pBR322 or YEp213. These are cloning vectors which have no expression signals, also the insert DNA does not have any expression signals therefore there is no expression of the protein. Choose an expression vector  -  Go to 34, 36 or 38. N.B . Another possible reason for the absence of expression is that the gene may have been inserted into the vector in the incorrect orientation, therefore is unable to use the vectors promoter sequences. If the sequence or restriction map of the gene is known then restriction mapping can be used to determine whether this is the case. © Annette Cashmore, GENIE CETL, University of Leicester Card-based problems (5)
83 SUCCESS Well done !!!! You have successfully produced your protein and it is biologically active. Producing a cell that synthesises large amounts of a desired protein is only the first stage in achieving a useful process. It is important to be able to recover the protein by a simple, economical method that results in high yields of a biologically active protein.  Cell cultures can be scaled up and grown in large fermentors, and then the protein can be purified using a number of methods. © Annette Cashmore, GENIE CETL, University of Leicester Card-based problems (6)
TV footage – why?  Familiar visual medium Can be used to: - convey information - as discussion starters Clips save time over full programme University  of Leicester
What sort of programmes?  Horizon, e.g. - Who’s afraid of designer babies? (2005) - The dark secret of Hendrik Sch ö n (2004) Drama documentaries, e.g. - Born with two mothers (Channel 4, 2005) Other drama, e.g.  - The Simpsons (e.g. Trash of the Titans) - The family man (BBC1, 2006) News clips - topical - pithy summary University  of Leicester
Therapeutic cloning Discussion after the clip could be taken in a number of directions: The science of therapeutic cloning including difficulties The ethical dilemmas including moral philosophy   Public understanding of science, the responsibility of scientists and media University  of Leicester
Knowing what’s on and when  Radio Times (other listings magazines are available) www.trilt.ac.uk     Television and Radio Index for Learning and Teaching But, news isn’t not known in advance! Today programme (Radio 4) BBC website, esp. Health sub-section University  of Leicester
Getting hold of programmes & clips  Off-Air Recordings Back-up  www.bufvc.ac.uk/services/offair.html   British Universities Film & Video Council Institutions set their own fee, e.g. at Leicester: - £1.50 for off-air at time of transmission - £10 for use of the BUFVC back-up service - Rates per hour for editing &/or converting   to different format University  of Leicester
Think of as many ways as possible that you might link one or more of the following news stories to your teaching of: (a) basic bioscience and/or  (b) bioethics?   Hwang cloning scandal Bird flu Herceptin Images from http://news.bbc.co.uk/ Using News stories in Bioscience
Cancer biology  Cell cycle control H uman  e pidermal growth factor  r eceptor (HER2) Monoclonal antibodies Therapeutic antibodies Resource allocation Clinical trials Herceptin
Therapeutic cloning  Research ethics Science of  stem cells Fraud Ethics of stem  cells research Hwang cloning scandal
Mode of action (Neuraminidase inhibitors)  Should wild birds be culled? Medicines: Tamiflu (Oseltamivir), Relenza (Zanamivir) Public perception of risk Bird flu  Virus biology Limited drugs/vaccines: who gets them first?
References  Southgate C. (2002)  The use of the rainforest as a test case in environmental ethics, in  Bioethics for Scientists  (Ed: Bryant, Baggott la Velle and Searle) Willmott C. (2004)  Ethics and Bioethics  Bioethics Briefing No. 1  (LTSN/ Higher Education Academy Centre for Bioscience), available online at  http://www.bioscience.heacademy.ac.uk/resources/ethicsbrief.htm Willmott C (2006)  Never again shout, “that WOULD have been useful for my teaching!” at the TV  Bioscience Education E-journal   7 -C1, available online at http://www.bioscience.heacademy.ac.uk/journal/vol7/beej-7-C1.htm   University  of Leicester

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Putting bioscience into context

  • 1. Dr Chris Willmott Dept of Biochemistry University of Leicester [email_address] Putting bioscience into context: exercises to enhance engagement Society for Experimental Biology (Canterbury) University of Leicester
  • 2. Outline of session ‘ Problem-based learning’ in Biology “ How does my course content relate to the outside world?” Examples – some mine, some others University of Leicester
  • 3. Outline of session Case studies/ scenarios Debate and role-play Card-based problems TV programmes, inc. Structured activity based on news footage Clips from other programmes Knowing what’s on and when University of Leicester
  • 4. Case Study (1) - Carl J. At age 5, viral myocarditis (inflammation of heart muscle) Developed prolonged and worsening heart difficulties (dilated cardiomyopathy) Now aged 12, Carl easily becomes tired and is frequently breathless; he cannot walk far A heart transplant is his only hope of survival No human donor has become available, but there is a trial programme using pig hearts Would YOU advise Carl’s parents to put him forward for the trial? Why/why not? University of Leicester
  • 5. Case Study (1) - Carl J. Example comments include: “ He’s going to die anyway, so why not give it a try” “ Yuk!” “ What about animal rights?” These comments are brought into discussion at relevant point in subsequent discussion e.g. risk of viral infection means more than just safety of individual patient at stake University of Leicester
  • 6. Case study (2) – Wendy & Paul Wendy and Paul Carter have been married for twelve years. They would love to have children. Unfortunately, Wendy had breast cancer when she was 28 and although the chemotherapy has brought total remission from the disease it also caused damage to her ovaries that have made her infertile. Paul and Wendy have been on the waiting list at their local IVF clinic for a number of months awaiting donated eggs to try and have a baby. At present, however, there are 200 potential mothers seeking each donated egg and the couple know that realistically they may never receive a donated egg via the normal channels. Researchers at the hospital attached to the IVF clinic have recently gained permission to carry out experimental procedures using eggs harvested from aborted foetuses. The technique is controversial, but for Paul and Wendy it may represent their only chance to receive a donated egg. University of Leicester
  • 7. What are the issues involved in this case? - Feel free to include aspects of the case that are likely to be issues for other people, your contributions need not be limited to your own opinions. Case study (2) – Wendy & Paul University of Leicester
  • 8. This case - content is fictional but based on real ideas and statistics - used in Session 1 of 6 in bioethics series - used as vehicle to introduce more philosophical aspects Case study (2) – Wendy & Paul University of Leicester
  • 9. Deontological (first principles) Does a foetus have any rights? Does the “mother” have any rights or say in the upbringing of their “grandchild”? Should people be allowed to manipulate nature for their own gain? Consequentialist (outcomes) What would be the psychological effects on the child? If the child turns out to be “defective” then who is culpable? What is the likelihood of success? Case study (2) – example comments University of Leicester
  • 10. Pharmaceutical development (1) Concerned by news coverage of increasing MRSA infection rates, you and your fellow directors of SmartaPharma plc decide to develop a new antibacterial compound. What stages will you need to go through from your initial idea until you have an effective (and profitable) medicine available for patients? University of Leicester
  • 11. Pharmaceutical development (2) Scientific stages in drug development: - finding lead compound - in vitro testing - animal testing - clinical trials: stages - who? - how many? - how long? - why done? Image from http://www.sandc.com University of Leicester
  • 12. Pharmaceutical development (3) Economic and legal stages: - students always forget to file a patent! - permission to administer: - when? - who from? - marketing Image from http://www.foremostmachine.com University of Leicester
  • 13. Pharmaceutical development (4) Lead into discussion of: - drug lifetime - named v generics - patent extending - counterfeiting - why are drug companies actually moving AWAY from antibacterials? Image from http://industry.am.nsk.com University of Leicester
  • 14. Debate & role-play Traditional debate, “This house believes…” Role-play allows students to become more immersed in the scenario Example – Use of the rainforest (Southgate, 2002) University of Leicester
  • 15. Use of the rainforest UN Conference on Environment and Development Roles, representatives of: - Government in country - A logging company - Indigenous forest-dwellers - Subsistence farmers in the area - Cattle ranchers - A multinational chemical company - UN commission on Sustainable Development Southgate (2002) University of Leicester
  • 16. Other suitable role-play scenarios Pre-implantation Genetic Diagnosis - “Saviour sibling” Roles, e.g.: - specialist doctor - sick child - parents - genetic counsellor - pro-life campaigner Task set, might be: Write scientifically accurate sketch (as team), or Research role ready for improvised TV show University of Leicester
  • 17. © Annette Cashmore, GENIE CETL, University of Leicester Card-based problems (1) Production of Medically Important Proteins Using Recombinant DNA Techniques
  • 18. 8 © Annette Cashmore, GENIE CETL, University of Leicester Card-based problems (2) FLOW DIAGRAM OF CLONING A GENE You must now decide how to clone your gene : (1) cDNA library - Go to 9 (2) genomic library - Go to 10
  • 19. 36 © Annette Cashmore, GENIE CETL, University of Leicester Card-based problems (3) YEAST VECTORS YEp213 Multicopy, DNA plasmid Shuttle vector - bacterial and yeast origins of replication (ORI) 2µm sequences (ORI andSTB) Selective markers : Yeast : auxotrophic marker - LEU2 gene (LEU2) Bacteria : Ampicillin resistance (Amp R) Tetracycline resistance (Tet R) Cloning vector Go to 37
  • 20. YEAST-SUMMARY You have cloned your gene into a yeast expression vector. Check the table to see if you have expressed a protein. 76 © Annette Cashmore, GENIE CETL, University of Leicester Card-based problems (4) 78 yes Somatostatin genomic Hind III pJP31 78 yes Factor IX 78 yes hEGF 78 yes Somatostatin cDNA Hind III pJP31 81 no Any cDNA / genomic Bam HI YEp213 Go to Expression Protein Insert DNA Enzyme site Plasmid
  • 21. 81 FAILURE !!!!! You have not been able to express your gene in this host - vector system. The reasons for this are : You have cloned into pBR322 or YEp213. These are cloning vectors which have no expression signals, also the insert DNA does not have any expression signals therefore there is no expression of the protein. Choose an expression vector - Go to 34, 36 or 38. N.B . Another possible reason for the absence of expression is that the gene may have been inserted into the vector in the incorrect orientation, therefore is unable to use the vectors promoter sequences. If the sequence or restriction map of the gene is known then restriction mapping can be used to determine whether this is the case. © Annette Cashmore, GENIE CETL, University of Leicester Card-based problems (5)
  • 22. 83 SUCCESS Well done !!!! You have successfully produced your protein and it is biologically active. Producing a cell that synthesises large amounts of a desired protein is only the first stage in achieving a useful process. It is important to be able to recover the protein by a simple, economical method that results in high yields of a biologically active protein. Cell cultures can be scaled up and grown in large fermentors, and then the protein can be purified using a number of methods. © Annette Cashmore, GENIE CETL, University of Leicester Card-based problems (6)
  • 23. TV footage – why? Familiar visual medium Can be used to: - convey information - as discussion starters Clips save time over full programme University of Leicester
  • 24. What sort of programmes? Horizon, e.g. - Who’s afraid of designer babies? (2005) - The dark secret of Hendrik Sch ö n (2004) Drama documentaries, e.g. - Born with two mothers (Channel 4, 2005) Other drama, e.g. - The Simpsons (e.g. Trash of the Titans) - The family man (BBC1, 2006) News clips - topical - pithy summary University of Leicester
  • 25. Therapeutic cloning Discussion after the clip could be taken in a number of directions: The science of therapeutic cloning including difficulties The ethical dilemmas including moral philosophy Public understanding of science, the responsibility of scientists and media University of Leicester
  • 26. Knowing what’s on and when Radio Times (other listings magazines are available) www.trilt.ac.uk Television and Radio Index for Learning and Teaching But, news isn’t not known in advance! Today programme (Radio 4) BBC website, esp. Health sub-section University of Leicester
  • 27. Getting hold of programmes & clips Off-Air Recordings Back-up www.bufvc.ac.uk/services/offair.html British Universities Film & Video Council Institutions set their own fee, e.g. at Leicester: - £1.50 for off-air at time of transmission - £10 for use of the BUFVC back-up service - Rates per hour for editing &/or converting to different format University of Leicester
  • 28. Think of as many ways as possible that you might link one or more of the following news stories to your teaching of: (a) basic bioscience and/or (b) bioethics? Hwang cloning scandal Bird flu Herceptin Images from http://news.bbc.co.uk/ Using News stories in Bioscience
  • 29. Cancer biology Cell cycle control H uman e pidermal growth factor r eceptor (HER2) Monoclonal antibodies Therapeutic antibodies Resource allocation Clinical trials Herceptin
  • 30. Therapeutic cloning Research ethics Science of stem cells Fraud Ethics of stem cells research Hwang cloning scandal
  • 31. Mode of action (Neuraminidase inhibitors) Should wild birds be culled? Medicines: Tamiflu (Oseltamivir), Relenza (Zanamivir) Public perception of risk Bird flu Virus biology Limited drugs/vaccines: who gets them first?
  • 32. References Southgate C. (2002) The use of the rainforest as a test case in environmental ethics, in Bioethics for Scientists (Ed: Bryant, Baggott la Velle and Searle) Willmott C. (2004) Ethics and Bioethics Bioethics Briefing No. 1 (LTSN/ Higher Education Academy Centre for Bioscience), available online at http://www.bioscience.heacademy.ac.uk/resources/ethicsbrief.htm Willmott C (2006) Never again shout, “that WOULD have been useful for my teaching!” at the TV Bioscience Education E-journal 7 -C1, available online at http://www.bioscience.heacademy.ac.uk/journal/vol7/beej-7-C1.htm University of Leicester