Hemoglobin Project
Background: Linus Pauling introduced the concept of molecular disease originating from chemical differences in proteins, demonstrating that the gene for sickle cell anemia was directly related to a variant of hemoglobin in the red blood cells of affected individuals. This variant was found to have a single amino acid replacement at position six of the beta chains of sickle cell hemoglobin (HbS). The sequence of the remaining 145 amino acids of the beta chains and all 141 amino acids in the alpha chains of hemoglobin were unchanged compared to normal human hemoglobin (HbA).
There are now >1500 different clinical mutations known to affect the stability and function of hemoglobin, and that number grows every year. While many of these are single-nucleotide-substitution mutations, deletions, and insertions that may be benign in effect clinical effects, the consequences of others vary from benign to severe, as for example is the case of some thalassemia. Many biochemists have made careers studying these hemoglobinopathies. A list of known human hemoglobin variants can be found at:
http://globin.cse.psu.edu/globin/html/huisman/variants/contents.html
The purpose of this project is to investigate a specific hemoglobin variant as the basis for a 5-page well-organized report: Page number is not including title page, figures, or citation list. Writing is to be double-spaced (Times New Roman 12pt font). The variant you will research and write about this year is:
Hb Thionville
Your report should have the following elements:
A description of the genetic mutation and its consequences for hemoglobin structure, function, and stability. (Your report must clearly indicate the original article first describing the variant hemoglobin).
Incorporate computer-generated images of the three-dimensional structure of the hemoglobin variant showing the precise location, or region, of the molecule affected. Be sure that the illustration is concise, clean, and informative and has an explanatory caption to go with it (figure caption are expected to emulate JBC [Journal of Biological Chemistry] guidelines). Other illustrations/figures can be included to supplement your text.
A brief overview of scientific writing, PDB, and PyMol will be given during the tutorial session on the weeks of:
February 26th – February 28th
March 4th – March 6th
There will only be time for a brief overview of PyMol functionality, i.e. students are expected to do much self-teaching during the duration of the semester. There is no shortage of succinct tutorials for PyMol on YouTube. Please have PyMol downloaded before the second of the two project specific tutorials:
https://pymol.org/2/
Describe any clinical and functional effects of the hemoglobin mutation (make sure that your sources are referenced!).
Provide citations to all references and illustrations (if not original) using the standard citation format of JBC. Part of the purpose of this assignment is for you to demonstrate your ability to find, use, and properly document information from the library (PubMed). Include at least, and preferably more than, five relevant citations from the primary literature.
Provide some general relevance by relating it to general protein structure and function principles, native human hemoglobin, and other human hemoglobin variants.
This should include the following aspects, but is not limited to*…
-How many amino acids are there in hemoglobin normally? How many are there in the variant? –Are alpha helices present in Hemoglobin? How many? Beta sheets? etc.?
-Hemoglobin is a tetramer. What are the names of the subunits?
-How many amino acids are there in each subunit?
-What is the prosthetic group in hemoglobin?
-Is the prosthetic group hydrophobic or hydrophilic?
-How is the prosthetic group attached to the protein?
-Where is the location of variation?
-How does the variation relate to structure and function of the protein?
*These are starting points to help stimulate your analysis, but many more interesting points/questions can be addressed
NOTE:
This ultimate purpose of this paper is to introduce you to the process of scientific writing
You will be evaluated for its composition, clarity of language/presentation, and biochemical analysis
An “A+” paper goes well beyond simplistic reporting of information
Molecular graphics representation of the hemoglobin variant chosen, showing the location of mutational modification, and its effect on higher-order structural elements is absolutely necessary! But make sure your prepared illustrations supplement your discussion, i.e. show something worth seeing!
This should be your synthesis of the information and not a paraphrasing of the words of others! This should not just be a report of the factual information your references have provided
This is not the “typical” writing assignment that you might have done in the past! So do not treat it as such. The intent is for you to do your very best work. The report you turn in should demonstrate that you truly understand and can apply what you have learned in this course. It should reveal your ability to reflect on a scientific topic and communicate it visually and in concise and precise way.
Suggestions for initial reading & guidelines for JBC formatting:
1. Nobel Prize winner, Max Perutz (1914-2002), spent 20 years working on the X-ray crystallography of hemoglobin before he finally determined its three-dimensional structure in 1957. Thereafter he spent much of the rest of his life studying the structure of interesting hemoglobin variants. To start the project, you might want to search and examine the publications of Max Perutz on PubMed or the Web of Science
2. Visit the data bases listed below and explore their reference lists and tabulations of hemoglobin variants:
NCBI (National Center for Biomedical Information), PDB (Protein Data Bank)
Swiss-Prot (Swiss protein data base)
3. https://www.jbc.org/content/authorinfo
4. https://paperpile.com/s/the-journal-of-biological-chemistry-citation-style/
PROJECT RUBRIC:
Basic outline for your Hemoglobin Project
Title
Introduction (Focus on necessary background information and significance of analysis)
Description of hemoglobin
Description of the genetic mutation and its consequences for hemoglobin structure, function, and stability
Description of clinical effects
Indicate the original article describing the variant
Discussion (Focus on Details)
Reference a computer-generated image of the 3D structure showing the region of the molecule affected
Discussion relating the mutation to protein structure and function in comparison to native human hemoglobin and other variants
Concluding paragraph
This is not a recapitulation of your introduction or a summary of your discussion, a good conclusion should place the analysis you have discussed into a broader biological context
References (JBC format)
Appendix of figures and tables (including properly formatted descriptions) *
*Figures can be attached to an appendix section of your paper after the reference list, or interspersed throughout your discussion. Both are acceptable, and in either circumstance, the figure does not count towards your 5-page limit.
Dealbreakers
Time of submissions: No late submissions accepted. Only one submission allowed, no retractions.
Minimum five primary literature citations: Must cite at least five primary articles with original findings.
5-page maximum (not including references and appendix of figures and captions): Any writing (title, introduction or discussion) beyond the 5-page limit will not be marked.
Plagiarism: Do not copy from other authors or other students. This is different from citing references. Plagiarism is copying sentences or paragraphs without proper requiting and acknowledgement of sources.
Criteria
Distinguished
(90-100%)
Proficient
(70-89%)
Passable
(50-69%)
Unacceptable
(below 50%)
Title (5%)
Concise, yet captivating. Detailed enough to adequately describe the topic of the paper, stated in a single sentence.
Clear but does not properly describe the paper or simply lacks creativity; stated in a single sentence.
Not clear; stated in a single sentence.
Incomplete, unfocused, or absent.
Introduction (10%)
Well-organized and conscientious description of native hemoglobin and the variant. Professional scientific writing, targeted at a biochemistry research audience. Clear description of purpose of the discussion.
A good attempt (broad and diverse range of references) is made as to why the topic is pertinent but may be slightly unclear or lacking in insight. Clear description of purpose of the discussion.
May be unclear (contain many vague terms), appear unoriginal, or offer relatively sparse description.
Little reference to the topic, audience or relevance.
Discussion content
(15%)
Clear examples to support specific topic sentences and to support the overall purpose. Writer answers most guideline questions and provides their own analysis and hypotheses. Cited information is well integrated with depth of coverage, without being redundant.
Examples support most topic sentences and support general purpose. Writer answers most guideline questions and provides their own analysis and hypotheses. Topics adequately addressed, but not in the depth expected.
Examples support some topic sentences; reader gains little insight; The essay shows little of the writer’s own analysis, relying instead on quotes and paraphrasing. Writer answers most of the questions posed in guidelines.
The essay relies on stringing together quotes or paraphrasing; Failure to support statements with major content.
Discussion organization
(15%)
The ideas are arranged logically to support the purpose. Transitions link paragraphs logically. It’s easy to follow the line of reasoning. Subheadings used throughout the paper allowing the reader to move easily through the text. Paragraphs have solid topic sentences.
The ideas are arranged logically to support the central purpose Transitions usually link paragraphs. For the most part, the reader can follow the line of reasoning. Subheadings are used throughout the paper to guide the reader without undue confusion; a few paragraphs without strong topic sentences.
In general, ideas are arranged logically, but sometimes ideas fail to make sense together. The reader is fairly clear about what writer intends. While subheadings are used, the content beneath them does not follow; many paragraphs without topic sentences.
Ideas are not logically organized. Frequently, ideas fail to make sense together. The reader cannot identify a line of reasoning. Subheadings not used. Few or no topic sentences.
Writing tone
(15%)
Consistently professional and appropriate, resembling what you would find in a review paper. Use of jargon that is appropriate to the field.
Generally, well written with few awkward phrasings.
Not consistent with expectations of university level writing.
Immature vocabulary and transitions reminiscent of high school writing. Riddled with grammatical errors and paragraph-long sentences.
Concluding paragraph
(10%)
The writer makes succinct and precise conclusions based on the review of literature. Suggestions for future research offered.
Some of the conclusions, however, are not supported. Suggestions for future research offered.
Some of the conclusions, however, are not supported; weak or trite suggestions for future research.
There is little or no indication that the writer tried to synthesize the information or draw conclusions based on the literature; no suggestions for future research.
Reference Quality (JBC format)
(10%)
References are primarily peer reviewed professional journals, reviews or other approved sources. These are properly cited throughout the paper.
Although most of the references are professionally legitimate, a few are questionable (e.g. textbooks, internet sources). These are properly cited throughout the paper.
Most of the references are from sources that are not peer reviewed and have uncertain reliability.
There are virtually no sources that are professionally reliable. Over-reliance on tertiary sources.
Figures and captions
(20%)
A variety of well-constructed figures to support each major point of analysis and demonstrate the structural features of the variant, with proper captions and descriptions.
Figures are clearly captioned and referred to within the paper to support parts of analysis.
Figures are clearly captioned and referred to within the paper, but may contain errors in construction or interpretation.
Figures with ambiguous captions, not well described in paper.
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