Makeup topics from first 2 lectures:

L1-Europa: gravitational forces, energy generation, and potential for extraterrestrial life.

L2-Mutations revealing gene functions:

Loss of function. Temp-sensitive mutations. Accumulation of metabolic intermediates. Domain swapping. Systematic alteration of a.a. sequences.

Endosymbiont hypothesis (Lynne Marguilis). How does DNA transfer from "bacterium-like" endosymbiont to main chromosome?

Paul Berg and "junk DNA" wager. Why do puffer fish have so little "junk" DNA? Prokaryotes: "wall-to-wall exons".

Model organisms: Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster.

Cell Biology Lecture 3 overview

Blackboard: many students = zero total score. Notice: Wed. = test date, so, if you hope to learn this information before then, must attempt Blackboard!

Read assignment, study it, then, attempt Blackboard quiz with book open. Purpose of Blackboard assignments: to help you learn. Please don't work to defeat this purpose!

Basic chemistry: protons, neutrons in nucleus. Electron orbitals surrounding nucleus. Vary protons=different elements. Vary neutrons=different isotopes. Radioisotopes easily detected.

Outermost electron shell = determine chemical nature of element. Most stable = complete outer shell. Ionic bonds: electron transferred, charges attract. Covalent bonds: share electrons.

Atom that "hogs" electrons = slight negative charge. Other atom = slight positive (polar).Water weakens ionic, hydrogen bonds; not van der Waals attractions. (Weak bonds important for molecular recognition). Mole, 1 molar, 1 millimolar solutions.

Four families of small organic molecules:

1.sugars (polysaccharides)

2.fatty acids (fats[6x as much energy w/w as glucose], lipids [amphipathic=hydrophobic + hydrophilic], membranes)

3.amino acids (proteins)

4.nucleotides (nucleic acids)

Condensation (dehydration synthesis), hydrolysis reactions. General formula of an amino acid.

Polymers 1 and 2 = energy-bearing. 3 and 4 = information-bearing. Is the ability to create fat a "good thing"? NCTR credo: "...it's not the fat, it's the calories."

Portion of NIH Request For (grant)Applications (October, 2000)-

RESEARCH OBJECTIVES: Background: Numerous studies in laboratory animals have shown that chronic caloric restriction (CR), i.e., limiting caloric intake below ad libitum levels, extends maximum and average life span by as much as 40% and delays age-related pathologies correspondingly. CR increases life span whether initiated in early adult life or middle age, but its effects diminish with increasing age of onset of CR.

http://grants1.nih.gov/grants/guide/rfa-files/RFA-AG-01-001.html Another site: http://www.healthypeople.gov/ CRAN: Caloric Restriction with Adequate Nutrition

http://scienceweek.com/2004/sb040820-4.htm

ScienceWeek CELL BIOLOGY: YEAST AND AGEING

The following points are made by S. Nemoto and T. Finkel (Nature 2004 429:149):

1) Yeast would seem an unlikely model system for learning about human ageing. A single-celled organism, essential perhaps for our daily bread and our favorite brew, it seems to lack the complexity that we associate with higher-order functions such as ageing. Nonetheless, yeast "replicative lifespan" -- a measure of the number of divisions a mother yeast cell can undergo -- has become a useful surrogate for mammalian ageing. Early in life, a mother yeast cell can readily divide, asymmetrically, to produce a daughter cell. Later on, when the mother cell has divided many times, it begins to enlarge and its capacity to produce progeny diminishes. The fact that middle-aged yeast as well as middle-aged humans are generally slower, fatter and less interested in reproduction provides our first (albeit broad) clue that certain biological markers of ageing -- and so, perhaps, the underlying mechanisms -- might have been conserved during evolution.

2) So what determines how many times a mother yeast cell can divide? Numerous environmental and genetic determinants have been identified. Among the environmental factors are several non-lethal stresses, for example reducing the glucose levels in the growth medium from 2% to 0.5%; such "caloric restriction" can significantly increase the replicative lifespan of yeast. This concept of "less is more" when it comes to calories and longevity is a theme that we see again and again, from yeast to mice.

3) In yeast, low-glucose conditions extend lifespan through the action of a gene termed SIR2 (1). Strikingly, a similar lengthening of lifespan ensues when yeast are simply manipulated to produce too much of the protein product of this gene(2). This product, Sir2, was first identified as a protein that modifies the physical state of DNA, causing a phenomenon known as genetic silencing ("Sir" stands for "silent information regulator"). Most evidence now supports the idea that Sir2 extends lifespan in yeast by regulating gene expression or suppressing recombination (the exchange of chunks of DNA between chromosomes), although the relevant genetic targets of Sir2 are unknown.

4) But what is the link between caloric restriction and Sir2? The protein's effects on DNA are achieved through its histone deacetylase activity -- its ability to remove specific acetyl groups from histones and other proteins that wrap up DNA. This activity of Sir2 in turn depends on the cellular levels of nicotinamide adenine dinucleotide (NAD) (2). NAD and its reduced form, NADH, represent a sort of basic energy currency in cells. Caloric restriction in yeast might increase Sir2 activity by altering either the NAD:NADH ratio or the levels of the NAD derivative nicotinamide. In other simple organisms, such as the fruitfly Drosophila melanogaster, caloric restriction might not only increase the activity of Sir2, but also directly regulate its levels(3). Increased Sir2 levels and activity might then dampen gene expression and recombination, leading (somehow) to an extension in lifespan.(4,5)