1. Determinants of Health and Disease (7.295) Srunphut Pukma
Lecture 1: Drug Development, Protein Synthesis, Cell Biology, Genetics, Hutchinson Gilford Progeria Syndrome

2. Introductions!
Welcome to MIT/BOSTON!!

3. 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.

4. Determinants…of Health Care and Disease?
What!!?? I didn’t sign up for Linear!!...
What is the definition of Determinants..?

5. Unmet Medical Needs

6. Biochemistry Review Inorganic Chemistry Cell Biology Genetics
Electronegativity
Polarity (Charged and Uncharged)
Cell Biology
Membranes
Protein Synthesis
Protein Trafficking and Modification
Genetics
Genotype, Phenotype, Mutation (Sporadic)
Anatomy and Physiology

7. Periodic Table of Elements
General Chemistry
Periodic Table of Elements

8. 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

9. The Water Molecule (H2O)

10. Electronegativity
The tendency for an atom to attract (take/accept) electrons onto its valence shells to gain “Stability”.

11. Hydrogen Bonding

12. Water “loving” or “hating”
Hydrophilic ~ having functional groups to “ATTRACT” Water mol.
Hydrophobic ~ having functional groups to “REPEL” Water mol.

13. **Discussion Question**
Could you think of some examples in “Nature” that you commonly see Hydrophobic/Hydrophilic interactions?

14. Amino Acids (Polar, nonPolar, Neutral)

17. Protein Structure

18. The Human Cell

19. Membrane Bi-layers

20. Nucleus and Nuclear Membrane

21. Chromosomes

22. Rough ER and Smooth ER

23. Ribosome Units

24. Protein Synthesis

25. Genetic Transcription

26. Genetic Translation

28. **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: _________________________________

29. Protein Modification

30. **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

31. Case Study: Hutchinson Gilford Progeria Syndrome

32. Hutchinson Gilford Progeria Syndrome

33. Nuclear Lamina and Envelop

34. Lamin-A Maturation

35. Progeria’s Nuclear Lamina

36. Lonafarnib (FTIs)

37. **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.

38. 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.