BIO 3342, Spring 2021
The purpose of this assignment is to provide you with an opportunity to apply what you have learned in BIO 3342 to understanding clinically relevant disease states using primary texts. As you know, in the Honors College we believe in analyzing original data rather than solely relying on textbooks to tell us what to think or believe. Your assignment is to choose a disease with a known molecular mechanism of pathology and identify two original research articles that helped establish the molecular explanation for the disease state. You will also need to gather other background information sources concerning the disease so that you can discuss its symptoms, spread or inheritance, and impact on survival. With these pieces of information, you are to write a 1,500 word paper. The paper should describe the cellular and molecular mechanisms that cause the disease pathology, focusing on the two foundational reports you select. Particular emphasis is placed on your presentation of the data included in the 2 research articles. Your paper should include an appropriate number of references but references are NOT included in the 1,500 words. A 1,500 word paper is approximately five pages, double-spaced in 12 pt Times New Roman font with 1 inch margins.
NOTE: I HIGHLY suggest reading the “Term Paper Rubric S21” document before you proceed with the remainder of these instructions. Very detailed instructions on the types of articles/information you should present are included, as well as detailed information about how you will be graded.
How to choose a disease for this project?
- Consider diseases that you would like to learn more about
- To ensure that you choose a disease about which enough is known concerning its molecular basis, you must select a disease that is mentioned within your textbook. (In previous semesters I did not use this limit, and students ‘got lost’ in the process of trying to understand the molecular mechanism(s) of diseases like idiopathic autoimmune disease or multigenic cancers with gene-environment interactions. Too many unknowns, too many factors, too much for this project. You may, however, choose a disease, like Alzheimers. The molecular mechanism underlying Alzheimers is not entirely agreed upon but you may discuss either of the prevailing models.)
- If you choose a disease of the immune system or a cancer, be sure that you choose a highly-defined, single-gene (or single driver gene) disease. For example, ‘breast cancer’ is far too broad, whereas inheritance of BRCA mutations and risk of breast cancer is acceptable (though still more complex than other genetic diseases). In general, I will caution you against these topics if your time to devote to this assignment is limited. I will also caution you against mood disorders and addiction for similar reasons, though the molecular basis of psychotropic drugs could be explored.
- It is perfectly acceptable to dive more deeply into a topic mentioned briefly in class already
Suggested categories of diseases/topics
NOTE: “Topics of Human Interest” found prior to Chapter 1 in your textbook may also be useful):
- Protein folding problems (i.e. Alzheimer's disease, Creutzfeldt-Jakob disease and Parkinson's disease)
- Infectious diseases (bacterial or viral infectious diseases):
- The ability to produce toxins (such as enterotoxin produced by Cholera)
- Cell adhesion (leukocyte adhesion deficiency, p. 259)
- Binding to specific cellular receptors for entry (Ebola, AIDS, and Tuberculosis etc.)
- Too much or too little of the essential nutrients (such as Type I diabetes: unable to regulate blood glucose levels, scurvy, or birth defects due to a lack of folic acid)
- Disease of the ECM (i.e. arthritis, osteogenesis imperfecta, dwarfism)
- Defective ion channels and transporters (i.e., cystic fibrosis)
- Diseases that impact muscles or neuronal signaling (i.e. Duchenne’s Muscular Dystrophy, Multiple Schlerosis, Myasthenia Gravis)
- Atherosclerotic narrowing of the arteries due to plaque deposition
- Poisonings (i.e. Organophosphate pesticides; Warfarin; tetrodotoxin; carbon monoxide; alkaloids like nightshade-derived atropine, hemlock-derived coniine, and curare; aflatoxin; cardiac glycosides of oleander; mushroom poisons like phalloidin, and many more!)
- Diseases due to epigenetic changes (I,e. alpha-Thalassaemia, Fragile X syndrome, etc)
- Genetic mitochondrial diseases
- Diseases thought to be related to endoplasmic reticulum stress (sleep apnea, Alzheimer’s disease, multiple sclerosis, ALS, possibly bipolar disease)
- Infectious diseases (bacterial or viral infectious diseases):
How to gather general information about your chosen disease:
- I suggest that you begin this project by learning about the disease, generally. Use reputable sites like: https://rarediseases.info.nih.gov or https://www.mayoclinic.org/diseases-conditions to get a basic understanding of the disease symptoms and characteristics. Additionally, foundations that support research concerning the disease can be good sources of information. If you use news articles, use highly regarded news sources like Reuters, New York Times, etc. Any website that sells a product alongside explaining a disease mechanism is not to be trusted.
- The assignment requires you to reference at least 1 reliable web site (e.g. government or university sponsored)
- Next, read scientific review articles. Authors of review articles use information from numerous original research articles to synthesize a comprehensive overview of our understanding of the disease at a given point in time (you must use reviews from the past 1-5 years, not older.)
- The assignment requires you to reference at least 3 review articles
- To find the scientific review articles, use Pubmed (https://www.ncbi.nlm.nih.gov/pubmed/). Sometimes journals produce a short report or a news article about research on diseases (for example, News and Views in the journal of Nature and news from Scientific American). Often the main scientific journals like Science or Nature offer accessible reviews of a particular topic (web sites: http://www.nature.com/browse/index.html?area=lifescience, http://www.nature.com/news/index.html, http://sciencenow.sciencemag.org/ ). These news and reports are often easy to read and interesting. Also, Nature Reviews produces excellent review articles. You may search this journal directly. You may also use books that are related to your disease of interest. However, this is not necessary. In summary, your research should include a search for general disease information and news reports, in addition to a Pubmed search for review articles from journals. These references should help you learn about your disease. But, book references are entirely optional.
- Finally you will draw background context from original research articles
- The assignment requires you to reference at least 4 original research articles in addition to the 2 original research articles that you will highlight in the body of the text
How to select the two original research articles to feature in your term paper:
- After you have read several good review articles, decide which original research articles represented the most pivotal studies that advanced understanding of the molecular mechanism of the selected disease. For instance, you might select a paper wherein the gene mutation underlying a disease is identified and the impact on the encoded protein is measured biochemically. You might select a paper wherein scientists described the first mouse model of a human disease (i.e. characterization of a knockout or transgenic mouse that develops cystic fibrosis.) Another option would be to explore a paper wherein a gene involved in pathology is overexpressed in cells and the impact on cell morphology and behavior is examined. A paper of good caliber and of importance to our understanding of the disease will be cited frequently in the background of subsequent original research articles and in review articles or textbooks.
- Review articles ARE NOT original research articles. The original research article presents the original data with materials and methods descriptions that explain how the data was collected. Review articles or news articles simply refer to these findings without showing the data or how the studies were conducted. Review articles discuss the findings of numerous experiments from numerous studies.
- Typically, landmark, pivotal studies like the ones you seek for this project are published in high-profile journals like Nature, Cell, Science, Proceedings of the National Academy of Science, Cancer Research, Journal of Biological Chemistry, etc. The articles you select should either be published in one of these high profile journals or should themselves be highly cited articles. Your librarian (Ms. Vedana Vaidhyanathan Vedana_Vaidhyanathan@Baylor.edu ) can help you determine if you have selected a respected journal or journal article. Your librarian can also show you how to use Zotero to manage your references for this paper.
- NOTE: Articles wherein the crystal structure of a protein is the primary finding are not suitable for the purpose of this term paper.
- NOTE: You may only use a study of human populations if it is inclusive of molecular data. For example, an article describing the identification of the mutation that underlies a genetic disease is only acceptable if the authors go on to show WHY and HOW at the protein level the mutation leads to disease. As another example, an article describing blood levels of a toxin in people who are exposed occupationally is not acceptable unless the authors go on to show how the poison is impacting the cells molecularly.
- NOTE: The textbook appendix “Additional Readings” found on pages A-1- A-6 catalogs the key journal articles used to write Chapters 1-17 of the textbook. Even if these articles aren’t suitable for this assignment, they may direct you to articles that are suitable (scan the bibliographies for promising titles.)
- NOTE: Where feasible, I recommend PNAS or Journal of Biological Chemistry articles over Science, Cell or Nature because they are more “readable” for novices.
This is not a full research paper; it is not possible to comment on every angle of the disease. Concise summaries will be key. The paper should focus primarily on describing the mechanism of the disease and two particular original research articles. When choosing your disease topic, be certain that it is a well-documented disease and that the cellular and molecular mechanisms that cause the disease are known.
I recommend using an outline to guide your writing. Begin with a basic sketch of the outline and as you read, fill it with pertinent details and associated citations. I recommend using the rubric to build your outline.
- Briefly introduce your disease, its symptoms, age of onset (if applicable), who it affects, and any other information that you think is important for the reader of your paper to know. This should be NO LONGER than two short paragraphs (one-half page).
- Describe what is known about the cellular and molecular mechanism of your disease. This may require up to two pages to outline, depending on how much is known.
- Explain, individually and in turn, the two papers you have selected. These papers should be selected to highlight the generally accepted mechanism of the disease. Again, you are looking for pieces of work shed great insight into how disease occurs at the molecular/cellular level. Your explanation should include: an outline of the model used to study the disease (mouse, cells, recombinant proteins), the hypothesis and independent and dependent variables studied, and the primary findings. This section should be the bulk of your paper (2-3 pages).
- NOTE: I have given specific instructions in the rubric for how to explain the two papers you have chosen. The primary source of deductions for students who wrote these papers last spring was in how the independent and dependent variables were presented and how the conclusions were presented. To receive full credit, follow instructions outlined in the rubric.
- Briefly restate/summarize the disease you selected and **how the specific papers you highlighted either contributed to our understanding of the disease or used mechanistic information to propose a novel molecular treatment**. This should be accomplished within one-half page.
- Write in your own words. The paper will be submitted to TurnItIn to detect plagiarism. Quotes from journal or review articles are not acceptable in scientific writing.
- Include citations in the body of your paper (cite the reference after the end of the sentence or paragraph, i.e. (1) and a list of references in a separate page. Use the PNAS style of citations: https://www.pnas.org/page/authors/format.
- DO NOT MAKE CLAIMS WITHOUT CITATIONS. Every claim must be cited.
Term Paper Grading Rubric
|Section||Criteria||Points award and deduction|
|Title Page and File Title 1 page 2 pt||Concise and descriptive title First and last name Course name Date submitted Save as .docx file with file name firstname_lastname_topic||+1 pt for a title page that includes all items listed in criteria +1 pt for a file tile containing your first and last names and a one term descriptor of topic -0.5 pt for each missing item|
|Brief Introduction to the Disease <0.5 page 5 pts||Introduce the disease you have chosen. Your introduction should include the primary clinical features, age of onset (if applicable), who and how many it affects each year, whether it is inherited or acquired, whether environment affects disease risk. Include any additional information that is required to orient the reader to the disease or aspects of the disease you will expand on in later sections||+5 pt for an introduction that addresses each item listed in criteria -2.5 pt for writing more than 0.5 page -0.5 pt for each incomplete, run-on or non-sensical sentence -0.5 pt for each piece of information presented without a citation|
|Mechanism by which Disease Pathology Occurs 1-2 pages 10 pts||Concise overview of the molecular and cellular mechanisms that lead to the disease Complete sentences in paragraph form Clearly written with a logical flow Adequate citations for all information presented||+10 pt for a thorough explanation of how the disease develops mechanistically from infection/entry/exposure/gene inheritance/birth to onset of disease symptoms -0.5 pt for each incomplete, run-on or non-sensical sentence -0.5 pt for each piece of information presented without a citation|
|2 Original Research Articles Regarding the Disease Etiology or Novel Treatment 2-3 pages 15 pts||Concise description of the studies presented in each of 2 original research articles (not review articles) you chose to highlight Two seminal journal articles that, when published, represented major advances in our understanding the molecular *mechanism* whereby the disease develops Keep description of analytical techniques brief Highlight the primary model used to characterize the cellular or molecular mechanism of the disease or to test the drug effect, the study hypothesis (hypotheses), the independent and dependent variables and the primary findings (you must focus on at least two data figures from each article, explaining each using the guidance provided in the column to the right) It is critical that the independent and dependent variables are clearly described, as this is a major reflection of your understanding of the factors being tested and how they are being tested NOTE: you do not need to highlight every experiment presented, rather identify and present the most important figures/findings. Identification of the key 2-3 figures reflects your comprehension of the work. Describing the study and findings within 1-1.5 pages requires concise writing—a key skill.||+15 pt awarded for thorough, concise and accurate explanation of the model used, hypotheses, independent and dependent variables and major findings for each of the two articles presented -no credit will be given for presentation of review articles -5 pt per article for not choosing the 2-3 most impactful figures and further explaning -0.5 pt for each incomplete, run-on or non-sensical sentences -2 pt each time the student fails to identify the research model organism/research paradigm utilized -2 pt each time the student fails to identify the most important independent and dependent variables for a data set/figure within the hypothesis statement. This should be clearly stated as follows: “The authors hypothesized that ___(independent variable)____ would increase/decrease the effect of __(dependent variable)_______ on _____________. OR The authors hypothesized that there was no effect of _______ on ____________. ” -2 pt each time the student fails to clearly state the findings derived from a particular data set/figure. The findings should be stated in a manner similar to: “Because of __(evidence)___,the authors’ findings suggest that the (independent variable) impacts (dependent variable) by ________.” *It is okay if your writing seems formulaic when the rubric is following. Using the guidance above will help you clearly articulate understanding of the experiments and data.|
|Summary of Material Presented <0.5 page 5 pt||Recap the findings from the 2 articles you highlighted in the context of what is known about the disease This section should include only findings that you described in the body of the paper Clear and concise (no more than one paragraph)||+5 pt for clear and concise summary of what you learned about the disease mechanism and how you conclude that the articles illuminate the disease mechanism -0.5 pt for each conclusion with no link to the mechanisms or articles discussed in the body of the essay -0.5 pt for each incomplete, run-on or non-sensical sentence -2.5 pt for writing more than 0.5 page|
|References 3 pt||References are properly cited after the end of a sentence or paragraph At least 10 references (8 general information references and the 2 highlighted original research articles) including at least:3 review articles1 reference to general information from reliable web sites (e.g. government or university sponsored)4 original research articles All references in PNAS format (see assignment page for details)||+3 pt for properly prepared reference section -0.5 pt for each reference that is incorrectly formatted -0.5 pt for each reference that is listed out of order of appearance in the essay|
Note: 1,500 word maximum, maximum of 5 pages, 12 pt Times New Roman double-spaced paper with 1” margins. Cover page and a reference page are not included in the word/page counts.