Louis Stodieck Phone: 492-4010 E-mail: stodieck@colorado.edu Office: ECAE 113

1. Louis Stodieck Phone: 492-4010 E-mail: stodieck@colorado.edu Office: ECAE 113

2. Lecture Notes Website www.colorado.edu\ASEN\asen5426

3. Reading Assignments “Molecular Cell Biology”, Lodish, Berk, Zipursky, Matsudaira, Baltimore and Darnell, 2000.

4. Control via Cells and Tissues • Controls emanate from cell form and function • 10-100 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

5. Constituents of Cells • Water (70-80%) • Ions (Na+, K+, Ca2+, PO4-, Cl-, etc.) • Carbohydrates (sugars, starches) • Proteins (chains of amino acids) • Structural vs. enzymatic • Soluble vs. membrane bound • Lipids (membranes, energy) • Nucleic acids (DNA, RNA)

7. Intestine – Epithelial cells

8. Trachea – Epithelial cells

9. Pancreas – Acinar cells

10. Kidney – Podocytes

11. Adipose cells

12. Blood – Erythrocytes

13. Muscle fiber

14. Nerve fiber – Schwann cell

15. Human Genome • 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!!!!

16. More Gene Trivia • 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)

22. Protein Synthesis a.k.a Translation

24. Comparison of Mammalian vs. Yeast Gene Structure

26. From: Hammond et al., 2000, Physiological Genomics, 3:163-173.

27. Control of Cell Division • Why is control necessary • Unchecked growth would be disastrous • 1 cell = 4.2(10)-9 g • Assume cells divide once each day • N = 2t (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

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

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

33. G1 Checkpoint • 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

35. 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)