HONR 210-01A: FALL 1997


Dr. Henry Jakubowski

Day 11,Wed, October 1

Today we discussed the structure of proteins. Proteins, like DNA, do not form a long linear chain -like structure, but rather fold in 3D space to form a unique structure. The same intermolecular forces that we studied for small molecules apply within the same molecule (i.e. in an intramolecular fashion), causing the protein to fold. Polar O's and N's like to be on the surface where they can H-bond to each other or water. Alternatively, if they are buried, they H-bond to each other. Nonpolar amino acid side chains prefer to be buried in the protein, interacting with other nonpolar side chains through London Forces. Charged side chains (+ for Lys and Arg, and - for Glu and Asp) are almost always found on the outside where they can interact with water or themselves, but occasionally are found buried only if adjacent to an oppositely charged side chain. Remember a couple things about big proteins:

If a mutation in a DNA causes a nonpolar amino acid to be substituted for a charged amno acid, the protein will most likely not fold correctly and hence lose biological function, since the charged amino acid, if intially buried, would likely be stabilized by an oppositely charged amino acid side chain. The converse is also true. If the change occurs on the surface, the protein would probably fold correctly. However, it might lose function if the changed occured in a binding site of the protein.

Day 12, Fri, October 3

We discussed the Immnune System. The two most important features is that the IS must recognize all foreign molecules (antigens) - the "enemy" (which might be on the surface of a bacteria, a virus, a virally infected cell, a cancer cell, or circulating molecules unattached to cells) but not recognized all self molecules. When self-recognition occurs, autoimmune disease occurs. .

Two major types of immune cells exist: B cells and T cells. B cells bind antigen through membrane bound antibody "receptor" molecules, and ultimately differentiate to form plasma cells which secrete antibodies into the circulation. T cells biind antigen through the T cell receptors. Antigen is often "presented" to the immune cells by cells called macrophages, which are cells that can actually engulf bacteria and other "foreign-looking" cells. The common motiff in immune cells when exposed to antigens is to

  1. bind - the antigen
  2. be stimulated -in which the inside of the cell responds by changing gene expression, dividing, and/or differentiating
  3. secrete - either antibodies for B cells, perforin for cytotoxic and natural killer T cells, and interleukin 2 for T helper cells.

.When T helper cells bind, through the T helper cell receptor, antigen fragments presented on the surface of macrophages, the T helper cell is stimulated to divide and also to secrete "lymphokine" (protein produced and secreted by lymphocytes) such as interleukin 2 which binds to other T cells and helps stimulate their division and secretion of perforin, which facilates killing of the target cell which is bound to the T cell. The T helper cells also secrete lymphokines such as B cell Growth Factor (BCGF) to stimulate B cell stimulation.

Day 13, Tues, October 7

The immnune system must not recognize self. How does it accomplish this? Two ways are used.

Elimination of all self-reactive T cells early in matuation

Binding of foreign antigens presented on unique cell surface proteins called the Major Histocompatability Complex (MHC)..

Day 14, Thurs, October 9

Student-led discussions of scientific method/process.

Day 15, Tues, October 14

Finish Student-led discussions of scientific method/process. We discussed how drugs are developed. Historically, the major way drugs have been discovered is by randomly seaching interestng mixtures of biological molecules, and determinng if any of the mixtures has a biological effect (on a whole organisim, a cell, or an isolated protein from the organism). Mixtures that possess biological activity are then purified (by chromatography) to find the specific agent within the mixture that demonstrates the activity. Its structure is then determined. Chemist then modifiy the structure of the active molecule is confer on it better medicinal properties (activity, solubility, lifetime, absorption, etc.). The second method can be called rational drug synthesis. In this technique, the 3D structure of the target is known. Computer modeling and analysis can be used to determine the geometry and chemical properties of a small candidate drug molecule which might bind to specific pockets or cavitites in the protein, whichn then might inhibit the function of the protein.

Day 16, Thurs, October 16

Exam 1

Day 17, Mon, October 20

We finished the last method of drug discovery, combinatorial synthesis. In this method, millions of different drug candidates are sythesized in one reaction vessel, or on discrete sites on silicon chips. Molecules that inhibit a protein can be "fished" out of the mixture from the vessel by washing the mixture of these synthesized molecules over a column containing beads to which the protein is linked, or localized on the silicon chip by using a fluorescent version of the protein target.

We started our dicussion of the basis of Eastern Science and Medicine. By expanding our conceptions of ideas, we can come to a more complete of the ideas. We will try to view ideas in more than one way, at least in a dualistic way, as we try to understand the ideas. We discussed a number of ways of viewing ideas from dualisic frames of reference.

Day 18,Wed, October 22

I presented an overview of the history of China, Dynastic cycles, and discussed the development of Chinese language.

Day 19, Fri, October 24

I presented an overview of different Chinese philosophies/religions which have influenced the culture, politics, and development of science and medicine in China. These include:

Specifically we talked about Confucius and his follower Mencius, Taoist illuminaires, including Lao Tzu and Chuang Tzu, the Naturalist ideas of the 2 Forces and 5 elements, and Mo-Tzu, and the Mohist.

Day 20, Tues, October 28

I continued with the overview of different Chinese philosophies/religions which have influenced the culture, politics, and science thought. We talked about:the opposite views of Mencius and Hsuan Tzu, the Legalists, the differences/similarities between the Roman Empire and the Han Dynasty, the two golden ages of Chinese history, the Han and Tang Dynasties, the rise and spread and decline of Buddhism in China, the mixing of Taosist and Buddhist principles in Zen, and how invaders (military and religious) became incorporated into Chinese culture and society.

Day 21, Thurs, October 30

We finished our discussion of Chinese history as we covered Mongol (Yuan)and Manchurian invasions (Ching), and the inbetween Ming dynsasty, stressing the stability of the dynastic system, and how invaders became incorporated into the culture. The stability of the Ming period in comparison to the West is remarkable, but led to stagnation in scientific thought in comparison to the West.

We then relooked at the effects of Confucianism, Taoism, and Buddhism on the development of science.


Last update on November 4, 1997