Undergraduate Assignment 1: Constructing a Summary 

For your first assignment, you will summarize the results, conclusions, and significance of a research article. The purpose is to hone your reading comprehension skills, particularly for primary scientific works. The intended audience for your summary is college freshman majoring in biology. This means they have had high school science courses, but are not fluent in complex scientific terminology. 

Your paper should be 3-5 double-spaced pages, which totals approximately 750-1250 words (use Arial or Times 11-12 point font). Your summary should consist of 3 parts: introduction, summary, and conclusions. During section meetings, you will go over the two assigned articles and discuss the components of your paper. You will choose one of the articles to summarize. A rough draft will be due for peer review in section on February 24. A rough draft will be due to your TA on March 2, and final drafts are due after spring break on March 16. 

Introduction (~1 page): Begin your paper with a brief introduction to the topic covered in the primary article. This should include an explanation of major cell biology subject examined (i.e. apoptosis) and the model system(s) used with a description of strengths and weaknesses of the model. Use one-two review articles on your topic to support your claims. 

Summary (~2 pages): State the major conclusions of the primary article. Describe the most relevant experiments in layman terms. 

Conclusions (~1 page): In this final section you should put the relevance of the work into a broader context. Convey the significance of the work to humanity. 

References (<1 page): List of citations used in your paper. Citations should follow The Cell journal format. 

Articles 

1. Jason C. Young et al. Molecular Chaperones Hsp90 and Hsp70 Deliver Preproteins to the Mitochondrial Import Receptor Tom70. Cell (2003) 112: 41-50.
2. Moore, MS and Blobel, G.  The GTP-binding protein Ran/TC4 is required for protein import into the nucleus. Nature. 1993 Oct 14;365(6447):661-3. 

Writing sample: 

When ancient Egyptians used yeast to leaven bread and ferment wine, little did they know that yeast would be used by a future great civilization for scientific research. Yet in the past few decades, the yeast used for food culturing, Saccharomyces cerevisiae, has become an important model organism for biology researchers.

The yeast S. cerevisiae offers many attractions as a model organism. Not least among its benefits is that its genome was the first to be completely sequenced (Botstein). Of these sequenced genes, 31 percent have a robust ortholog among human genes, and at least 71 human genes can restore function to yeast cells with the corresponding gene deleted (Botstein). In aIDition to being genetically similar to humans, yeast are also easy to use in research. It is much easier and inexpensive to manipulate the yeast genome than to do the equivalent research in mammals (Botstein). Because of this ease of use and relevance to humans, yeast has become extremely popular in biological research.

One feature of S. cerevisiae makes it especially popular in the area of aging research: it exhibits observable aging, which is unusual for a unicellular organism. Bacteria were once thought not to age, and although they may age in some respects (Nystrom), the aging is not as obvious as it is in yeast. Yeast are much simpler and easier to manipulate than other organisms used to study aging, such as thefruit fly, roundworm, and mouse and are therefore a valuable model organism for aging.

Yeast aging is somewhat different from the aging of higher mammals (e.g. you can’t get wrinkles when you’re a single cell), yet it shows some general similarities. Like humans, yeast go through life stages: a “young” stage with logarithmic growth and glycolytic metabolism, a “mid-life” stage characterized by oxidative metabolism, and an “old” stage when the cells stop dividing, lower their metabolism, and become resistant to heat and oxidative stress (Tissenbaum). This is similar to how aging humans stop reproducing and have decreased rates of metabolism.

Interestingly, it has been found that in many species, lowering an organism’s metabolism by means of calorie restriction can lengthen its lifespan (Howitz). In yeast, calorie restriction promotes longevity by increasing the activity of the gene SIR2 (Howitz), a NAD-dependent histone deacetylse that silences several yeast chromatin loci, including telomeres, mating loci and ribosomal DNA (rDNA) (Tissenbaum). Silencing rDNA prevents it from recombining with itself and generating extrachromosomal rDNA circles (ERCs), which replicate with each cell division and can accumulate at toxic levels in aging yeast cells. ERCs seem to be related to aging, and SIR2 might lenghten lifespan at least in part by lowering the rate of ERC formation (Guarente, Howitz, Tissenbaum).

So why does calorie restriction increase SIR2 activity? Reducing calories decreases how much NAD is used in the glycolytic pathway, making more available for the NAD-dependent activity of SIR2 (Sharpless). This might explain why calorie restriction increases lifespan and why a single extra copy of SIR2 can mimic calorie restriction in yeast (Howitz). If an extra gene in yeast can reproduce the effects of calorie restriction, could this approach work for humans? Perhaps there’s a way to reap the longevity benefits without actually restricting calories. Sirtuins, the family of NAD-dependent histone deacetylases of which SIR2 is a member, might be the answer. Compounds that activated these molecules might help to postpone aging and age-related disorders (Sirtuins).

Luckily, researchers have been looking for—and finding—sirtuin activators. A few years ago, researchers at BIOMOL Research Laboratories and Harvard Medical School searched for small molecules that activate the sirtuin SIRT1, the human analog of SIR2. They found that the plant compounds resveratrol, quercetin and piceatannol were strong activators of SIRT1 (Howitz).

First, the authors screened small molecule libraries for molecules that affect sirtuin activity. They used a fluorescent deacetylation assay to measure SIRT1 activity and compared the activity with no compounds aIDed (the control) with the activity when a molecule was aIDed. They found that 25 micromolar resveratrol increased SIRT1 activity by a factor of 13.4 +/- 1.0. Piiceatannol and quercetin increased activity by factors of 7.9 +/- 0.50 and 4.59 +/- 0.47, respectively. Other molecules that activated SIRT1 were butein, isoliquintigenin, and fisetin (Howitz).

Next, the researchers studied whether these compounds that activated SIRT1 actually increased the lifespan of living organisms. Doing this research in humans would have taken decades, so the researchers took advantage of yeast as a model organism for aging and studied the compounds in yeast. Three compounds, butein, fistein, and resveratrol, increased the average yeast lifespan by 31%, 55%, and 70% respectively (Howitz). Quercetin and piceatannol had no significant effect, but perhaps that was due to insufficient uptake of these compounds into the cells or oxidation in the medium (Howitz).

Interestingly, restricting the calories of cells already treated with resveratrol yielded no significant aIDitional increase in lifespan (Howitz). This suggests that resveratrol affects lifespan through the same pathway as calorie restriction (Howitz) and that researchers may have found the long-sought pathway responsible for the longevity benefits of calorie restriction. If activating sirtuins does indeed increase the lifespan of humans, perhaps we can enjoy longer lives … while still enjoying our food! 

References 

Botstein D, Chervitz SA. Yeast as a model organism. Science. 1997;277(5330). 

Guarente L, Kenyon C. Genetic pathways that regulate ageing in model organisms. Nature.2000;408:255-262. 

Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang L, Scherer B, Sinclair DA. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003;425:191-196. 

Sharpless NE, DePinho RA. p53 Good Cop/Bad Cop. Cell. 2002;110(1):9-12. 

Tissenbaum HA, Guarente L. Model Organisms as a Guide to Mammalian Aging. Developmental Cell. 2002;2(1):9-19.

Attachment:- Undergrad Paper Feb10.pdf