Unit 3 Biology: signatures of life conceptual framework Chemical nature of the cell The nature of molecules Interactions between molecules determine shape of biomacromolecules and produces binding sites for: enzymes and substrates Signals and receptors Antibodies and antigens Explains how: various materials enter and leave a cell Cells receive and respond to signals How the immune system works How vaccines work How we design drugs Much of Unit 3&4 biology explores the dynamic nature of the cell

Molecular biology in medicine EL: To explore the application of molecular biology in medicine.

Molecular biology Applications of molecular biology in medicine, include: Knowledge and manipulation of genetic material the development of designer drugs to: Prevent action of infective micro-organisms Inhibit the action of specific chemicals in the body the production of hormones and plant vaccines

Inherited diseases Also known as genetic disorders Exist because of defect in kind or amount of DNA in the affected organism Many different types Eg a whole chromosome may be involved or just a single gene (NB. We’ll only focus on single gene defects)

Inherited diseases Knowledge about the gene responsible may allow: Testing for the presence of the defective gene (eg breast cancer gene, phenylketonuria (PKU) Special treatment to delay onset of the disease Reducing severity of condition through treatment (eg cystic fibrosis) or special diet (eg galactosaemia, PKU)

Gene therapy The insertion of a normal functional gene into cells that contain a defect Two types: in vivo: gene therapy given directly to patient ex vivo: gene therapy in which the patient’s cells are manipulated outside the body and then returned into the individual The specially prepared functional piece of DNA inserted into the cell is called a cloned gene

Gene therapy

Viral Gene therapy A vector is used to carry the gene into a cell Most commonly used vectors are viruses Viruses with DNA replicate in the nucleus of the cells they infect Viruses with RNA replicate in the cytoplasm of the cells they infect Exception is RNA viruses called retroviruses – they also replicate in the nucleus Most commonly used vectors in gene therepy are retroviruses and adenoviruses

Retroviruses Only used in cells that are reproducing when nuclear membrane breaks down and chromosomes of infected cell become accessible Useful for cells that can be taken out an cultured outside the body (eg blood, bone marrow)

Adenoviruses DNA viruses – enters nucleus but remains separate from the host DNA The cloned DNA is functional and produces functional protein May be short-lived as this small piece of DNA doesn’t replicate when the host cell does

Adenoviruses

Viral Gene therapy Still experimental in humans and can pose risks to patients safety, eg Temporary solution Insertion into wrong place on chromosome, causing a different disease Immune response to virus

Non viral Gene therapy As yet, not very successful Methods include Transporting DNA into cells in lipid spheres Direct injection of DNA into cells Manufacture of artificial chromosomes

Medical diagnosis: Pre-Natal Testing Used to determine if baby has a genetic defect Done via: Ultrasound: physical defects Biochemical test on embryonic cells or amniotic fluid: metabolic defect

Medical diagnosis Obtaining a sample of embryo cells can be done through: Chorionic villus sampling: at 6-8 weeks Removal of a small piece of chorion tissue Amniocentesis At 16-18 weeks Collecting a sample of amniotic fluid surrounding the fetus

Medical diagnosis

Medical diagnosis: Presymptomatic testing Breast cancer: women with BRCA1 or BRCA2 gene have 80% risk of developing breast cancer (compared with 10% in rest of population) Tests exist for the gene an women who test positive may either: have their breasts removed before they develop the disease, or get regular mamograms

Rational drug design When a drug is designed to act against an infective agent: The molecular structure of the active site of the infective agent is established The drug is designed to have a complementary structure The drug locks into the active site to prevent development of the disease

Rational drug design When a drug is designed to inhibit the action of a chemical in the blood: The molecular structure of chemical is established The drug is designed to have a structure that locks into the active site of the chemical The chemical is inactivated

Rational drug design The delivery of vaccines in plant material as food involves: Determining the molecular structure of the proteins in the infective agent that cause the immune response Introducing the DNA that codes for these proteins into the plant genome Growing and harvesting the plants eg measles vaccine in powdered lettuce, cholera vaccine in rice

Manufacturing biological molecules Genetically engineering proteins that are deficient (eg insulin)

Nanoparticles Nanoparticles are: Manufactured 1-100 nanometers (one billionth of a meter) in diameter Made of a double layer of phospholipids to mimic plasma membrane of the cell Used to deliver toxic drugs directly to target cells (eg tumour cells), reducing the chance of affecting healthy cells

Activity/homework Complete the Molecular Biology exam questions Chapter 4 Quick Check qu 1-16

Reflection What did you learn about molecular biology today?