determinants of health and disease (7.295) srunphut pukma lecture 1: drug development, protein...
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Determinants of Health and Disease (7.295)
Srunphut Pukma
Lecture 1: Drug Development, Protein Synthesis, Cell Biology, Genetics,
Hutchinson Gilford Progeria Syndrome
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Introductions!
• Welcome to MIT/BOSTON!!
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What is this class about…?
• To better understand the current medical needs and problems.
• To understand the biological and chemical basis of multiple diseases.
• To develop a keen perception of the medical professions (doctors, nurses, PAs, ems…)
• To construct a strong sense of biological and medical research ethics.
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Determinants…of Health Care and Disease?
What!!?? I didn’t sign up for Linear!!...
What is the definition of
Determinants..?
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Unmet Medical Needs
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Biochemistry Review• Inorganic Chemistry– Electronegativity– Polarity (Charged and Uncharged)
• Cell Biology– Membranes– Protein Synthesis – Protein Trafficking and Modification
• Genetics– Genotype, Phenotype, Mutation (Sporadic)
• Anatomy and Physiology
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General Chemistry
Periodic Table of Elements
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The Atom! (Protons..Neutrons..Electrons)• Atomic compositions of
elements (Carbon Atom)• Nucleus (Proton + Neutrons)
• Protons are POSITIVE• Neutrons are NEUTRAL • Electrons are NEGATIVE
• Molecules form when two or more atoms are bonded through specific chemical connection
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The Water Molecule (H2O)
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Electronegativity
• The tendency for an atom to attract (take/accept) electrons onto its valence shells to gain “Stability”.
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Hydrogen Bonding
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Water “loving” or “hating”
• Hydrophilic ~ having functional groups to “ATTRACT” Water mol.
• Hydrophobic ~ having functional groups to “REPEL” Water mol.
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**Discussion Question**
• Could you think of some examples in “Nature” that you commonly see Hydrophobic/Hydrophilic interactions?
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Amino Acids (Polar, nonPolar, Neutral)
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Protein Structure
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The Human Cell
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Membrane Bi-layers
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Nucleus and Nuclear Membrane
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Chromosomes
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Rough ER and Smooth ER
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Ribosome Units
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Protein Synthesis
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Genetic Transcription
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Genetic Translation
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**Discussion Question**• What is the resulting PROTEIN Sequence?
DNA: A T C G A C T A A G G C A T A A T A G C A MRNA: _________________________________PROTEIN: _________________________________
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Protein Modification
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**Discussion Question**
• A special brain cell is making a protein, and where is bears a ABB-SBB consensus there will be a hydrophobic group attached. How will this protein look? Note, hydrophobic groups prefers to be in hydrophobic regions of the cell.
XXX-ABB-SSB-XXX-SSB-ABB-XXX-ABB-SSB-XXX
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Case Study: Hutchinson Gilford Progeria Syndrome
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Hutchinson Gilford Progeria Syndrome
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Nuclear Lamina and Envelop
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Lamin-A Maturation
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Progeria’s Nuclear Lamina
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Lonafarnib (FTIs)
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**Discussion Question**• Drug design is a vital component of treating a disease
or illness. When considering certain therapeutic treatments, many factors must be regarded (age, weight, sex). Discuss the following phrases: Agree/Disagree? Why/Why Not?– It is important to use multiple drugs to treat a disease.– People of the same age could consume the same drugs.– Specific drugs only serves specific purposes.– Killing animals is cruel, we should not use them to test drugs
or medicine.– Famous medicines should never lose their patents. –
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Medicinal Treatments: Case Study• Think like a chemist! You need choose drug(s) that will help
ameliorate the conditions of Progeria. 7 year old Sally Bloom, as other progeria patients, complains of problems with her fragile bones, her lack of body fat, and too much bad cholesterol (LDL). Design a treatment plan for Sally.
Drug Name: Treatment Side Effects/Common Results.
Bone Plus 3000 Helps strengthen bones, skeletal muscle, and teeth.
Causes lost of appetite for children under 5 years old.
F-Lipid X Prevents farnesylation of Lamin-A. Decreases Subcutaneous Fats
Retinal AAA Helps improve eye sight and eye health. NO Side Effects.
Calci-MAX Improves bone health. Increases LDL (Bad Cholesterol)
Lip-Detour Prevent farnesylation of Lamin-A. Increases HDL (Good Cholesterol)
OMEGA 91K Increase Subcutaneous Fats and Decrease LDL
Causes increase in Hair Growth on head.
Gamma-Gen Improve Alzheimer’s conditions Make bones brittle and breaks.