Genome 547- Scientific Writing

1. Genome 547- Scientific Writing All are agreed that the articles in our journals-even the journals with the highest possible standards-are, by and large, poorly written. Some of the worst are produced by the kind of author who consciously pretends to a ‘scientific scholarly’ style. [Many students begin graduate school with reasonable writing skills]… Two years [into graduate school] these same students’ writing is verbose, pompous, full of fashionable circumlocutions… The student can no longer write, he pontificates. What has brought about the change? Clearly the students have copied these dreary and pretentious phrases from the scientific literature. They have been dutifully studying it as they are urged to do, and it has warped their style to the point that they can no longer walk to the door without “utilizing a pedestrian relocation,” or sip their coffee without “prior elevation of the containing vessel to facilitate imbibation.” F. Peter Woodford, Editor of Science.

2. Writing is difficult. Dear Dr. Pallanck, Your piece was very long and wordy and I tried to slightly reduce some of the verbiage. I was careful to edit judiciously. I found your piece extremely repetitive in places. Sincerely, a PNAS editor Writing can get better. Dear Dr. Pallanck, Yours was one of the rare pieces that required little editing. I wish that more authors could write as clearly and with purpose. It was truly a pleasure to work with you. Sincerely, another PNAS editor

3. This course emphasizes general writing principles In past years the writing pertained to manuscripts This year, the writing will pertain to proposals (specifically, your oral exam proposal) Due in late spring quarter (May or June)!

4. How the course will be run: -Each week, I will provide you with a writing assignment -You will submit the assignment to me by email the following Saturday -I will then send all of the assignments to the entire class later that same day -You (with a partner) will edit the assignments in the next class, and discuss the changes you made -You will modify your writing to reflect the critique and turn it in to me the following week Each class session: ~1/2 hour of principle & 1.5-2.5 hours of editing Logistical issues: -All class material (Powerpoint files, course reading, etc.) will be posted online for download

5. Today: Grant applications

6. Written General exam format: The thesis proposal should be 12-15 pages long (double spaced in 11-point or 12-point font) not including additional pages of figures and references, organized as follows: Research Plan (1 page): Briefly describe the key issues and how you plan to achieve an experimental solution. You should specify one or more clear-cut hypotheses and define a few (2-5) Specific Aims that will enable you to test each hypothesis. Background (3-4 pages): Describe in detail how this problem has been studied in the past, what was learned, what remains unsolved, and why. Preliminary Findings (2-3 pages): Describe work you already have done on the problem and discuss your data. If relevant data are lacking, describe related kinds of work you have done and how the skills and findings learned from this work influences your plans for the proposed work. Methods of Procedure (3-4 pages): Detail the technical aspects of your planned work with regard to each of your Specific Aims. What specific experimental procedures will you employ? Where applicable, justify your use of the specific procedures chosen as opposed to others that may be available. Alternative Approaches (1-2 pages): You should be prepared in your oral examination to discuss how the broader scientific issues you are proposing to address in your work might be studied in another experimental system (preferably in another organism). Outline at least one such alternative approach here in your written preparation. Significance (1 page): How might you expect your future findings to advance scientific knowledge more broadly and/or benefit human welfare?

7. 1. Grant Applications How are grant applications organized? A. TITLE Often restricted in length (NIH: 81 characters, including spaces and punctuation). In general, you should avoid using abbreviations and jargon, other than generally accepted terms (DNA, mRNA, etc.). Include words that convey what you want to do and why it is important: Protein Ubiquitination in Cell Models of Disease. Genetics of New Synaptic Components and Their Functions. B. ABSTRACT The abstract should describe succinctly (~1/2 page) every major aspect of the proposed project except the budget. The abstract should ideally include: 1. A brief background of the project. 2. The hypothesis or hypotheses to be tested. 3. The tests of the hypothesis or hypotheses. 4. The significance of the proposed research.

8. C. SPECIFIC AIMS The purpose of the specific aims is to describe, in a single page or less, what the proposed research is intended to accomplish. Preparation of a research proposal usually begins here, although the abstract will come ahead of the specific aims section. The specific aims, and the abstract are the two most important parts of a grant application. These two sections will be the only parts of the proposal that some reviewers will read. The specific aims should ideally include: 1. The general goal and significance of the research (one to three sentences). 2. A theoretical model. 3. The hypothesis or hypotheses to be tested. This is nearly essential for successful funding! Make sure that you have a real hypothesis In your oral exam guidelines, this section is called the “Research Plan”

9. An example of what not to do: Alzheimers Disease (AD) is a dementing disorder of unknown etiology. The diagnosis of “presumed” or “probable” AD is made through clinical diagnosis, in recognition that AD can only be definitively diagnosed histopathologically. Characteristically, memory is initially impaired, followed by visuo-spatial deficits, and, finally, involvement of all cognitive functions. We hope to address a number of Specific Aims by the completion of this project: 1. Is there selective involvement of a particular component or class of cells in the visual system of AD patients? If so, can this be related to the pathophysiology of AD in the rest of the brain? If there is a predilection for loss of a class of ganglion cells in AD, this may yield insight to the reasons for predominant degeneration of large neurons in other areas of the brain. 2 Can visual testing be used, in conjunction with present neurological and psychometric evaluations, as a screening procedure to identify AD? 3. Can visual testing or histopathological assessments of the visual system be used to identify subtypes of AD? If so, this might provide insights leading to possible management and treatment strategies for AD. 4. We will gain insights into both anatomical and functional AD subgroups through correlative histopathological and clinical assessments of the visual system in the age-matched controls (normals) used in this study. 5. Significant new data relevant to the effect of age on the visual system will be gathered.

10. Good! An example of what not to do: Alzheimers Disease (AD) is a dementing disorder of unknown etiology. The diagnosis of “presumed” or “probable” AD is made through clinical diagnosis, in recognition that AD can only be definitively diagnosed histopathologically. Characteristically, memory is initially impaired, followed by visuo-spatial deficits, and, finally, involvement of all cognitive functions. We hope to address a number of Specific Aims by the completion of this project: 1. Is there selective involvement of a particular component or class of cells in the visual system of AD patients? If so, can this be related to the pathophysiology of AD in the rest of the brain? If there is a predilection for loss of a class of ganglion cells in AD, this may yield insight to the reasons for predominant degeneration of large neurons in other areas of the brain. 2 Can visual testing be used, in conjunction with present neurological and psychometric evaluations, as a screening procedure to identify AD? 3. Can visual testing or histopathological assessments of the visual system be used to identify subtypes of AD? If so, this might provide insights leading to possible management and treatment strategies for AD. 4. We will gain insights into both anatomical and functional AD subgroups through correlative histopathological and clinical assessments of the visual system in the age-matched controls (normals) used in this study. 5. Significant new data relevant to the effect of age on the visual system will be gathered.

11. Good! An example of what not to do: Alzheimers Disease (AD) is a dementing disorder of unknown etiology.The diagnosis of “presumed” or “probable” AD is made through clinical diagnosis, in recognition that AD can only be definitively diagnosed histopathologically. Characteristically, memory is initially impaired, followed by visuo-spatial deficits, and, finally, involvement of all cognitive functions. We hope to address a number of Specific Aims by the completion of this project: 1. Is there selective involvement of a particular component or class of cells in the visual system of AD patients? If so, can this be related to the pathophysiology of AD in the rest of the brain? If there is a predilection for loss of a class of ganglion cells in AD, this may yield insight to the reasons for predominant degeneration of large neurons in other areas of the brain. 2 Can visual testing be used, in conjunction with present neurological and psychometric evaluations, as a screening procedure to identify AD? 3. Can visual testing or histopathological assessments of the visual system be used to identify subtypes of AD? If so, this might provide insights leading to possible management and treatment strategies for AD. 4. We will gain insights into both anatomical and functional AD subgroups through correlative histopathological and clinical assessments of the visual system in the age-matched controls (normals) used in this study. 5. Significant new data relevant to the effect of age on the visual system will be gathered. Not useful No hypothesis No theory

12. Good! An example of what not to do: Alzheimers Disease (AD) is a dementing disorder of unknown etiology.The diagnosis of “presumed” or “probable” AD is made through clinical diagnosis, in recognition that AD can only be definitively diagnosed histopathologically. Characteristically, memory is initially impaired, followed by visuo-spatial deficits, and, finally, involvement of all cognitive functions. We hope to address a number of Specific Aims by the completion of this project: 1. Is there selective involvement of a particular component or class of cells in the visual system of AD patients? If so, can this be related to the pathophysiology of AD in the rest of the brain? If there is a predilection for loss of a class of ganglion cells in AD, this may yield insight to the reasons for predominant degeneration of large neurons in other areas of the brain. 2 Can visual testing be used, in conjunction with present neurological and psychometric evaluations, as a screening procedure to identify AD? 3. Can visual testing or histopathological assessments of the visual system be used to identify subtypes of AD? If so, this might provide insights leading to possible management and treatment strategies for AD. 4. We will gain insights into both anatomical and functional AD subgroups through correlative histopathological and clinical assessments of the visual system in the age-matched controls (normals) used in this study. 5. Significant new data relevant to the effect of age on the visual system will be gathered. Not useful No hypothesis No theory Weak!

13. Good! An example of what not to do: Alzheimers Disease (AD) is a dementing disorder of unknown etiology.The diagnosis of “presumed” or “probable” AD is made through clinical diagnosis, in recognition that AD can only be definitively diagnosed histopathologically. Characteristically, memory is initially impaired, followed by visuo-spatial deficits, and, finally, involvement of all cognitive functions. We hope to address a number of Specific Aims by the completion of this project: 1. Is there selective involvement of a particular component or class of cells in the visual system of AD patients? If so, can this be related to the pathophysiology of AD in the rest of the brain? If there is a predilection for loss of a class of ganglion cells in AD, this may yield insight to the reasons for predominant degeneration of large neurons in other areas of the brain. 2 Can visual testing be used, in conjunction with present neurological and psychometric evaluations, as a screening procedure to identify AD? 3. Can visual testing or histopathological assessments of the visual system be used to identify subtypes of AD? If so, this might provide insights leading to possible management and treatment strategies for AD. 4. We will gain insights into both anatomical and functional AD subgroups through correlative histopathological and clinical assessments of the visual system in the age-matched controls (normals) used in this study. 5. Significant new data relevant to the effect of age on the visual system will be gathered. Not useful No hypothesis No theory Weak! Could be combined as a hypothesis and test Subtypes of AD? Depends on outcome of Aim 3 Aim 5 is not really an aim

14. A better version: Alzheimer’s Disease (AD) is a dementing disorder of unknown etiology. Recent studies have shown that AD is associated with loss of larger brain cells and with optic nerve degeneration. Since the retina is actually part of the brain and has been studied in far greater functional and anatomical detail, it may provide an ideal model in which to investigate the relationship of cell’s size to its susceptibility to damage in AD. Specific Aims: 1. We will test the hypothesis that large neurons are selectively destroyed in AD by measuring the sizes of ganglion cells in the retinas of AD patients and in age-matched controls. 2 A corollary of this hypothesis suggests that large ganglion cell-dependent visuomotor function of AD patients should be defective. We will test this hypothesis with eye-track recordings in patients and in age-matched controls.

15. Problem and significance A better version: Alzheimer’s Disease (AD) is a dementing disorder of unknown etiology. Recent studies have shown that AD is associated with loss of larger brain cells and with optic nerve degeneration. Since the retina is actually part of the brain and has been studied in far greater functional and anatomical detail, it may provide an ideal model in which to investigate the relationship of cell’s size to its susceptibility to damage in AD. Specific Aims: 1. We will test the hypothesis that large neurons are selectively destroyed in AD by measuring the sizes of ganglion cells in the retinas of AD patients and in age-matched controls. 2 A corollary of this hypothesis suggests that large ganglion cell-dependent visuomotor function of AD patients should be defective. We will test this hypothesis with eye-track recordings in patients and in age-matched controls.

16. A theoretical model A better version: Alzheimer’s Disease (AD) is a dementing disorder of unknown etiology. Recent studies have shown that AD is associated with loss of larger brain cells and with optic nerve degeneration. Since the retina is actually part of the brain and has been studied in far greater functional and anatomical detail, it may provide an ideal model in which to investigate the relationship of a cell’s size to its susceptibility to damage in AD. Specific Aims: 1. We will test the hypothesis that large neurons are selectively destroyed in AD by measuring the sizes of ganglion cells in the retinas of AD patients and in age-matched controls. 2 A corollary of this hypothesis suggests that large ganglion cell-dependent visuomotor function of AD patients should be defective. We will test this hypothesis with eye-track recordings in patients and in age-matched controls.

17. A better version: Alzheimer’s Disease (AD) is a dementing disorder of unknown etiology. Recent studies have shown that AD is associated with loss of larger brain cells and with optic nerve degeneration. Since the retina is actually part of the brain and has been studied in far greater functional and anatomical detail, it may provide an ideal model in which to investigate the relationship of a cell’s size to its susceptibility to damage in AD. Specific Aims: 1. We will test the hypothesis that large neurons are selectively destroyed in AD by measuring the sizes of ganglion cells in the retinas of AD patients and in age-matched controls. 2 A corollary of this hypothesis suggests that large ganglion cell-dependent visuomotor function of AD patients should be defective. We will test this hypothesis with eye-track recordings in patients and in age-matched controls. The hypothesis and tests of the hypothesis

18. D. BACKGROUND AND SIGNIFICANCE The Specific Aims section of the proposal provides the reader with a general idea concerning the scope of the project, the technology involved, the logic of the experimental approach, and the hypothesis to be tested. However, these ideas were presented as unsupported statements, so a major goal of the Background and Significance section is to provide this support through expansion and judicious reference to the literature. Because the primary reviewers may not be familiar with the area of investigation, or the technology being used, it is also important to address these matters. However, the purpose IS NOT to be comprehensive: the purpose IS to present citations that build a solid foundation for your proposal. This section of the proposal needs to establish the following matters: The project is important. It relates to significant human disease or to a significant deficit in our knowledge of an important biologic process: the results of the hypothesis tests will have a predictable impact on theory and/or ultimately lead to improvement of the human condition. The project is interesting. The subject can be related to a general theoretical model that is the subject of widespread interest; important areas within the model that are unproven, controversial, or ambiguous are addressed. There is a high probability of success. Specific hypothesis to be tested can be identified as part of a theoretical model; tests of the hypotheses are feasible, definitive, and within the range of the PI’s apparent expertise.

19. Some suggestions: • -Begin this section with the importance of the project. • -Briefly describe what is known. • -Briefly describe what is not known. • -Be critical of earlier work in the field (but not meanspirited). • -Briefly describe what needs to be done. • -Briefly emphasize how your results will meet the stated need. • -Cite reviews sparingly-cite your reviewers (if not contrived). • -Often helpful to include a limited number of figures/tables summarizing complex information, or describing the models to be tested. • E. PRELIMINARY STUDIES • The purpose of the Preliminary Studies section is to describe (your) prior work that is relevant to the proposed project. • This section of the proposal needs to establish the following matters: • That you are fully competent in all of the procedures proposed • To establish beyond a reasonable doubt that the proposed studies are logical and feasible.

20. Technical/Editorial Considerations: • -Create subsections to address specific experimental goals. • -Figures and tables should be as uncomplicated as possible, and placed as close as possible to where they are referenced in the text. • -Figures and tables MUST be legible. • -Design each figure and table to convey a single point. • -Place methodology in the figure/table legends, NOT in the text. • Often this section makes or breaks a proposal. • F. RESEARCH DESIGN AND METHODS • This section of the proposal should tell the reviewers: • 1. What you propose to do. • 2. How you propose to do it. • 3. What results you expect and what they will mean in terms of the overall project. • 4. What might go wrong. • 5. What alternative approaches will be used to cope with potential problems.

21. Technical/Editorial Considerations: -The Research Design and Methods section should be divided into subsections, with each subsection corresponding to one of the specific aims of the proposal. -Each subsection (aim) of the Research Design and Methods section should be further subdivided as follows: Title: restate the specific aim, verbatim. Introduction: a short paragraph that states the objective of the aim, the hypothesis to be tested, the overall strategy and the expected outcomes. Experimental Design: describe the experiments that will be performed. Avoid emphasis on routine methods and trivial details (pH, buffer composition, etc.) unless the technology would be unfamiliar to the reviewers. This is not intended to be a methods manual. Anticipated Results and Potential Problems: summarize your most important results (but do not overstate expectations). If potential problems exist, state them, offer alternative strategies, but DO NOT overemphasize them. -Each subsection (aim) should be roughly equally weighted (each should consist of a similar number of pages in the Research Design and Methods section).

22. First writing assignment: The Research Plan (specific Aims) section of your written exam proposal. Due at 5:00PM this Saturday.