BE/APh161: Physical Biology of the CellHomework 1Due Date: Tuesday, January 11, 2010“The quality of a person’s life is in direct proportion to their commitmentto excellence, regardless of their chosen field of endeavor.” - Vince LombardiComments from RP to Class:In my view, homeworks are one of the primary tools at a teacher’s dis-posal to push an educational agenda. I am big on sports analogies, and thesimple fact is this: if you want to shoot free throws like Kobe Bryant youhave to practice your craft. It isn’t always amusing, but it pays off later. Asa result, I put lots of time into both thinking up problems and writing textthat goes along with those homeworks that I think will give you the oppor-tunity to practice things that will help you do science better later when it is“for real”. The reading that goes along with my homeworks is a key part ofthe course material, so please read my commentaries (and argue with themif you have an alternative perspective).This first homework has as its main objective the development of a feel forthe numbers associated with various biological problems and the beginningof an ability to use software for visualizing biological structures and examin-ing biological sequence information. This particular homework will probablyinvolve more searching around on the web than others. Please make sure toreport your sources.Referee report: Read the vignettes from the new book that I am writingwith Ron Milo entitled “Cell Biology By the Numbers” that are posted onthe course website associated with this homework and write a referee reporton each one. The report should focus on the following questions: Does theoverall logic make sense? That is, is the point of the vignette clear and doesthe organization work in making this point? What suggestions do you have tomake it more readable, clear and interesting? Did it teach you anything new?What would you suggest should be removed? Try to find extra biologicalnumbers pertinent to the vignette. Bonus: join the community effort andcontribute these numbers at www.BioNumbers.org1Please E-mail the report, as a Word or PDF file, to me ([email protected]),Yi-Ju Chen ([email protected]) and my coauthor Ron ([email protected])on the day the homework is due.1. Who Are You?In class I made the passing remark that you have more foreign cells in yourbody than those containing your own DNA. Make a simple estimate of thenumber of human cells you are made up of, the number of bacterial cellsyou harbor in your gut (assume there are 2 kg of bacteria in your gut), thenumber of human genes you carry and the number of genes associated withthe more than 200 different species of bacteria you are carrying around.2. Manipulating Atomic CoordinatesThis is basically prob. 2.4 of PBoC.Visualization of the various structures populating the cell is a key part of ful-filling the objective of structural biology to connect structure and function.In addition, having a sense of the sizes of the various molecular actors inthe cell will permit us to make the kinds of estimates that will run throughthe course. For example, later, we will consider gene regulation and willbe interested in how large a DNA sequence serves as the regulatory site forgenes of interest. Part of our answer to that problem will depend upon therelative sizes of proteins and base pairs. In this problem, you will learn howto manipulate pdb files from the Protein Databank and to view them usingone of the various plotting programs.(a) Obtain coordinates for the atoms in ATP, phosphatidylcholine, B-DNA, and the green fluorescent protein (GFP) provided with this homework.More generally, you can do this by visiting sites such as:“http://www.rcsb.org/pdb/home/home.do” (i.e. the Protein Data Bank).Give a brief description of each one of these molecules and its role in cellularlife.(b) Download a structural viewing code such as VMD (University of Illi-nois), Rasmol (University of Massachusetts) or DeepView (http://www.expasy.ch/spdbv/)2and create a plot of each of the molecules you downloaded above. You candownload one of these programs under the “General Interest” part of theAPh161 webpage. Experiment with the orientation of the molecule and makesure you print out pictures of each and every molecule. In each drawing, usethe tools provided within the software to provide relevant scale bars thatcharacterize the size of these molecules.3. Sugar Budget.The discovery of radioactivity revolutionized biology in a huge number ofdifferent ways. One way was that it showed that physicist’s estimates onthe age of the Earth were completely off base and hence that evolution hadhad far longer to act than originally thought. A second key outcome wasthat radioactive isotopes provided a means of following the paths of variousmolecules during their journey through the biochemical life of a cell. Indeed,the famous papers by Calvin on the biochemistry associated with photosyn-thesis were entitled “The Path of Carbon in Photosynthesis”. In addition,radioactivity provided a means of quantifying the number of molecules ofinterest on the grounds that there is a linear relation between the numberof radio labeled molecules and the intensity on a radiogram. Hence, overthe years, much effort has gone into counting up the number of molecules ofdifferent types in living cells. Ultimately though, there has to be a carbonsource and radioactivity has been a reliable tool in tracing the path of carbon(and other elements) in organisms.(a) Estimate the number of sugars to make an E. coli cell. Note that in class,we flirted with these kinds of estimates when we examined the constructionof a bacterium. Now, it is your turn to exploit this kind of estimation tosee what you come up with. Chap. 2 of PBoC should help you formulateyour estimate. Remember to carefully state your assumptions. Also, for themoment, concentrate only on the building materials needed to make a celland don’t worry about the energy needed to assemble them.(b) LB media is one of the famed growth media for studying bacterial cul-tures. However, for more controlled experiments, a growth medium with onlya single carbon source is used (so-called minimal media) which has 0.2 g ofglucose for every 100 mL of media. A typical experiment involves 5 mL of3minimal media which is inoculated with a small number of cells (let’s assumeone cell) which then grows and divides repeatedly until the culture saturatesat
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