BE 4930 / BE 5900 SPECIAL TOPICS: INTRODUCTION TO GENETIC ENGINEERING AND MOLECULAR MEDICINE

FALL 2000


Information Flow in Biology
Nucleus of an Atom
Elements Found in Organisms
BioChemistry
Electronic Structure
Ionic Bonds
(Electrons Exchanged)
Covalent Bonds
(Electrons are shared)
Hydrogen Bonds
Summary of Electrostatic Interactions
Water as a polar molecule
Acid - Base Chemistry
Amino Acids (aa)
Gly, Ala, Val, Leu, Ile, Pro
Amino Acids (aa)
Phe, Tyr, Trp
Amino Acids (aa)
Cys, Met, Ser, Thr
Structure of Proteins
b-Sheet and b-Turn
3D Structure of Proteins
H-bonds between DNA strands
Enzyme-Substrate Complex
KINETICS  OF  A  CHEMICAL  REACTION
(Activation  Curve)
CELL SIGNALLING
CELL ADHESION
ION  CHANNELS
FACILITATED  DIFFUSION
SODIUM / POTASSIUM  PUMP
PROTEIN  PATHWAY
GOLGI APPARATUS
ENDOCYTOSIS
MITOCHONDRIA
CYTO-SKELETAL FILAMENTS
CELL ATTACHMENT
CONTRACTILE   FILAMENTS
CONTRACTION  CYCLE
VOLTAGE  GATED  CHANNELS
TRANSVERSE (T)  TUBULES
GAP  JUNCTION
TROPONIN-C  &  G-PROTEIN
CELL CYCLE
Bacterial Cell Division
Cell Cycle
Duplicated chromosomes are separating
Sister chromatids
Mitosis vs Meiosis
Chromosomal arrangements during Meiosis
Principles of Mass Spectrometry
Collision with an electron (e-)
Output of the Mass Spectrometer
Electrophoresis
Principles of Dialysis
Ultracentrifugation
Absorption vs Phase Contrast
Optical Microscopy
H&E Stained Tissue Section
Fluorescent Microscopy
Optical Microscopy
(A) Transmission		
(B) Phase-contrast
(C) Differential-Interference-Contrast
(D) Dark-Field
Confocal Scanning Fluorescence Microscope
Electron Microscopy
F. A. C. S.
2D SDS Gel Electrophoresis
X-Ray Crystallography
Troponin-C and Ca++
Gel Serves as  Molecular Sieve
Electrophoretic Mobility
Ion Exchange Chromotography
X-Ray Crystallagraphy
Metal Shadowing to use TEM to get 3D images resembling SEM
Electrophoresis
Recombination
Crossing of Sex Chromosomes
Diploid Mapping
Drosophila Genome
Early Human Chromosome Map
Classification of Diseases
o  Congenital and 
Congenital and Hereditary Diseases
o Results of developmental disturbances
o Causes: Abnormalities in genetic material, number and distribution of chromosomes, intrauterine injury by various agents, environmental effects.
o Example: Congenital heart disease caused by German measles
Inflammatory Diseases
o Results of an injurious agent by means of inflammation
o Causes: Microbiologic agents such as bacteria, alergic reactions, hypersensitivity, auto-immune diseases
o Examples: Sore throat, hay fever, asthma
Degenerative Diseases
o Results of degeneration of various parts of the body
o Causes: Natural (aging), accelerated degeneration
o Examples: arthritis, arteriosclerosis 
Metabolic Diseases
o Resulting from a disturbance in some important metabolic process
o Causes: Malfunctions of endocrine system, imbalances of fluids and electolytes
o Examples: diabetes, parathyroid diseases
Neoplastic Diseases
o Resulting from abnormal cell growth causing benign and malignant tumors
o Causes: Genetic, environmental, viral
o Examples: All cancers.
Diagnostic Tests
o Clinical laboratory tests
o Tests that measure the electrical activity of the body
o Tests using radio-isotopes
o Endoscopy
o Ultrasound procedures
o X-ray examinations
o Magnetic resonance imaging
o Cytologic and histologic examination of cells and tissues removed from the patient
Clinical Laboratory Tests
o Analyte concentration measurements
o Clearance tests for renal function
o Pulmonary function tests ([O2] and [CO2])
o Microbiological tests
o Serological tests for ABY
Inflammatory Reaction
Chemical Mediators of Inflammation
o Mast cells in connective tissue, containing histamine
o Histamine: a potent vasodilator (increases permeability of vessels)
o Platelets ® serotonin (vasoconstrictor)
o Injured cells ® prostaglandins
o Blood plasma ® bradykinin
Immunity
o Humoral: Antibody (ABY) mediated
o Cell mediated: formation of population of lymphocytes which can attack and destroy foreign materials (first line of defense).  Also responsible for the rejection of transplants.
o Hypersensitivity: causes intense inflammation, anaphylactic shock (acute respiratory distress)
o Auto-immune disorders
Interrelationship of Cell-Mediated and Humoral Immunity
Pathogenesis of Allergy
Mechanism Thought to Cause Auto-ABY formation 

Congenital & Hereditary Diseases
Sex Chromosome Abnormalities
o FEMALES
- Turner's syndrome (XO) for 1/2500
- Triple X syndrome (XXX) for 1/850
o MALES
- Klinefelter's syndrome (XXY) for 1/750
- XYY syndrome for 1/850
DOWN'S Syndrome 
	(Trisomy of Ch21)1/600 births

Intrauterine Injury Caused by Thalidomide
Neoplastic Diseases
Factors Leading to Neoplasmic Transforma-tion of Cells
Immunotherapy for Cancer
o Non-specific: immunization of patients with various bacteria or bacterial products to stimulate their immune system
o Specific: administration of immunizing substances containing tumor cell antigens
Abnormalities in Blood Coagulation Pathway 
o Figure showing the coagulation and thrombolytic pathways
Cardiovascular Disorders
o Myocardial Infarction (1.5 million cases annually)
o Coronary Artery Disease
o Heart Failure (5 million cases, 5000 transplants/year)
o Number 1 cause of death in USA and EU
Myocardial Infarction
o Disturbance of cardiac rhythm (aka arrhythmias)
o Heart failure
o Cardiac rupture
o Intracardial thrombi
o Pericarditis (from inflammation)
o Papillary muscle dysfunction (loss of contractility)
o Ventricular aneurysm (bulging)
Coronary Artery Disease
Role of Cholesterol in CAD
Heart Failure (HF)
o Heart is no longer able to function efficiently
- Acute HF: rapid progression
- Chronic HF: slow onset and progression
o Pathogenesis
- Forward failure: Inadequate cardiac output resulting salt and water retention by kidney
- Backward failure: Blood backup in venous circulation
Respiratory Disorders
o Pneumothorax: Loss of negative pressure
o Atelectasis: Incomplete expansion of lung due to
- obstruction of bronchi
- external compression 
o Pneumonia (inflammation of lungs)
o Tuberculosis
o Emphysema (destruction of alveoli)
o Bronchial Asthma (IgE®bronchospasm)
Pancreas
o Islets of Langerhans
- a: secretion of glucagon (­[glucose])
- b: secretion of insulin (¯[glucose])
- D: inhibition of glucagon & insulin secretion
o Cyctic Fibrosis(CF gene on Ch. 7)
- 50% mortality before age 21
- Defective transport across cell membrane (Sodium, Chloride, Bicarbonate, Water)
- Thick mucus accumulation
- Obstructions in pancreatic ducts, bronchi and bile ducts ® cystically dilated ducts.
Diabetes
o Insulin dependent (Type I): Resulting from a damage or destruction of pancreatic islets, leading to reduction or absence of insulin secretion
o Non-Insulin dependent (Type II): Somatic cells are relatively insensitive to the actions of insulin
- More common
- Reason for impaired response is not known
- Correlated to obesity