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Reading Assignments DateLectureAssignment 4/1Cellular growth, division, differentiation and death Guyton Ch. 2 & 3 Lodish Ch. 13, p , p: /3Cellular responses to external signalsGuyton Ch. 74 Lodish Ch 20, p: , p: /8Breakdown of cellular growth control: Cancer Guyton Ch. 3 Lodish Ch. 24, p , p /10Insulin control of blood glucoseGuyton Ch. 78 Lodish Ch. 20, p: /15Calcium regulation and hormonal control of bone mass Guyton Ch. 79 Class Notes 4/17Cellular mechanisms and local control of bone mass Class Notes 4/22Control of skeletal muscle massGuyton Ch. 6, p:77-78 (10 th ed), p:82-83 (11 th ed); Ch. 84, p: (10 th ed), p: (11 th ed), Class Notes 4/24Effects of novel environments on physiological controls Guyton Ch. 43, Class Notes 4/29Applications in cell and tissue engineeringClass Notes 5/1Oral presentations 5/3Exam III (During final exam slot – 4:30pm) “Molecular Cell Biology”, Lodish, Berk, Zipursky, Matsudaira, Baltimore and Darnell, 2000.

Control via Cells and Tissues Controls emanate from cell form and function – trillion cells in the human body –Each cell carries a full blueprint (genome) but runs different subroutines (gene expression) –Integrated responses of cell aggregates (tissues and organs) give rise to whole organism responses

Constituents of Cells Water (70-80%) Ions (Na +, K +, Ca 2+, PO 4-, Cl -, etc.) Carbohydrates (sugars, starches) Proteins (chains of amino acids) –Structural vs. enzymatic –Soluble vs. membrane bound Lipids (membranes, energy) Nucleic acids (DNA, RNA)

Intestine – Epithelial cells

Trachea – Epithelial cells

Pancreas – Acinar cells

Kidney – Podocytes

Adipose cells

Blood – Erythrocytes

Muscle fiber

Nerve fiber – Schwann cell

Human DNA has 3.2 billion base pairs Data is equivalent to ~800 Mbytes –Only ~1.5% (12 Mb) codes for actual “products” Each cell (with few exceptions) contain 23 chromosome pairs Stretched out, DNA would be 6 ft. long for a single cell End to end, an individual’s DNA would reach to the sun and back 60 times!!!! Human Genome

Human genome has been sequenced –Humans have ~25,000 genes Yeast = 6,000 genes Fruit fly = 13,000 genes Nematode = 18,000 genes Arabidopsis = 26,000 genes –We differ from each other by roughly 1 base pair per 1000 (99.9% the same) More Gene Trivia

Protein Synthesis a.k.a Translation

Comparison of Mammalian vs. Yeast Gene Structure

From: Hammond et al., 2000, Physiological Genomics, 3:

Why is control necessary –Unchecked growth would be disastrous 1 cell = 4.2(10) -9 g Assume cells divide once each day N = 2 t (N = number of cells, t = time in days) In 1 month = 4.5 g In 2 months = 4,800,000 Kg = 5,000 tons –But cell division is necessary Developmental growth Maintenance of tissue and organ functions Repair of damaged tissues Immune cell proliferation Control of Cell Division

Mitosis – cell division ~30 min. to complete Prep for mitosis ~4-5 hours -DNA repair and “proofreading” DNA replication ~10 hours Prep for DNA replication Highly variable ~9 hrs. in cycling cells Postmitotic cells Quiescent phase

Controlled by cyclin-dependent kinases (Cdks) Cdks are made through transcriptional induction –Growth factors –Hormones –Tissue disaggregation –Mitogens Control of Cell Division

Cdks phosphorylate proteins (RB) that would otherwise inhibit cell cycling Phosphorylation causes short-term positive feedback – Threshold response (not unlike action potential) Other proteins can delay or stop process or redirect cell to apoptosis G1 Checkpoint

Apoptosis Cells commit suicide through programmed cell death Cells require trophic factors to prevent –Mechanism always armed –Binding of trophic factors alters phosphorylation –E.g., nerve growth factor (NGF) Final death agents are caspases (proteases)