Sunday, February 26, 2012

Future Bridges Lab Rules version 0.1

Lab Rules


Version 0.1.3 on July 14, 2012 by Dave Bridges

Remember when you were growing up and you would say, well when I’m older I will (or won’t) do that.
I have been thinking of that, for my future when I run my own group.
It is fairly easy (and as a bit of a blowhard I do this all the time) to say I would do this, or I would do that.
I think posting this publicly will encourage me to stick to these rules.
Below are some roles and a bit of rationale and caveats.
This is the first version of this post but future versions will include links to the previous versions.
The version numbering is described in the Lab Policies README.
Check out the GitHub Repository for more granular changes.

Supervision of Trainees

Trainee-Advisor Contract
Both myself and trainees (either mine, or co-supervised trainees) will read, discuss and sign a contract describing our roles and responsibilities both as a trainee/employee and a mentor. This will include data dissemination/publishing rules, expectations of productivity, note keeping and time commitment, rules for dealing with other members both in my group and in collaborations, rules for sharing of reagents and data, rules for adjucating disagreements and grounds and procedures for termination. These rules will be in conformity with any institutional rules. Exceptions can be discussed and the agreement can be modified throughout the term of the relationship. I will post a generic version of this agreement in a publicly viewable location.
Online Presence
All trainees will appear on the laboratory website and write a blurb about their research interests and goals. Trainees will be strongly encouraged to blog, tweet and otherwise engage in social networking tools regarding their research and the work of others, but this is not required. Links to their publicly available social network profiles will be posted on the laboratory website.
Open Access Policy
Trainees will be made aware of the open publishing, dissemination, software and data/reagent sharing policies of the laboratory at the outset and will have to agree to these standards.

Reagents, Software and Tools

Software Usage
Wherever possible, free open source software will be used for data acquisition, analysis and dissemination. Exceptions will be made if necessary, but trainees will be encouraged to use/incorporate/development free tools.
Software Development
If software, scripts or the like are generated they will be released under a permissible open source license such as CC-BY and the license will be attached explicitly to the source code. Scripts and programs will be uploaded to a public revision control database such as GitHub or similar (my GitHub profile is here).
Publishing of Protocols and Scripts
When not present in the published article, detailed step by step protocols, data analysis scripts and other things which cannot fit into either methods and materials sections or supplementary materials will be posted online and linked to the publication’s online presence (post or as a comment on the paper’s website).
Protocol Sharing
Protocols will be made available online in a wiki format in a publicly available location, whether they have been published on or not. Editing will be restricted to laboratory members and collaborators.
Reagent and Tool Sharing
Reagents generated by my group will be shared upon request without condition (aside from potential restrictions placed by other collaborators, funding agencies and the institution). These reagents will be shipped with an explicit statement of free use/sharing/modification. Once a reagent sharing license is generated/identified it will be linked to in this document. This policy includes unpublished reagents and will never require attribution as a condition. If a reagent is obtained from another group and modified, we will offer the modified reagent back to the originator immediately.

Publishing and Data Dissemination

Open Access Journals
I believe that all work should be available to the public to read, evaluate and discuss. I am strongly against the mentality that data/knowledge should be restricted to experts and the like. I will therefore send all papers in which I am corresponding author and have supervised the majority of the work to journals (or their equivalent) which are publicly available. The two major caveats will be for work in which I am a minor (less than 50% effort) collaborator and the primary group leader wants to submit the work elsewhere. This will not exempt any potential major impact publications, no matter how awesome they may be. Delayed open access does not count in this respect.
Open Peer Review
Journals will be selected which publish non-anonymous reviewer comments alongside the articles whenever possible. If this is not done, and if permissible by the publisher and/or reviewers I will re-post the reviewer comments online without any modifications.
Public Forum for Article Discussion
Although I will encourage discussion of articles to occur at the point of publication (for example via the posting of comments directly at the website of the publisher), I will also provide a publicly available summary of every published finding from which I am an author (corresponding or not) and allow commenting at that point too. This discussion post will also link to or contain the reviewer and editor comments where possible. This summary might be a blog post, a facebook post or a google plus post or anything else that might come up in the future. If I am not the primary author or corresponding author I will encourage the first or corresponding author to write the post and link/quote that directly.
Presentations
All presentations of published data will be posted on an online repository such as Slideshare or something similar. My slideshare profile is here. If unpublished or preliminary data is presented privately and then is later published, then those slides will be presented upon publication. Similar to papers, an online blog post or the like will also accompany that upload. If audio or video of the presentation is available, that will be uploaded as well.
Data Sets
All datasets, once published will be made available in manipulable (preferably non-proprietary) formats for further analysis. Based on the scheme set out by the Linked Data Research Center Laboratory, all data will be provided at level 2 or above.

Sunday, February 5, 2012

Chickens and Eggs

Yesterday two posts appeared in my feed both challenging the requirement of glamor mag (Nature, Science, Cell) level publications for career advancement.  Michael Eisen (@mbeisen) wrote a post in response to this idea suggesting that this is not a criteria for hiring in his experience (he is referring to job applications where he is, at UC Berkeley as well experiences with his  trainees).  Key point:

My own lab provides several examples that demonstrate this reality. My graduate students have gone on to great postdocs and many have landed prestigious fellowships “despite” having only published in open access journals. More curiously, I have had four postdoctoral fellows go out onto the academic job market, who  all got great jobs: at Wash U., Wisconsin, Idaho and Harvard Medical School. Not only did none of them have glamour mag publications from my lab. None of them had yet published the work on the basis of which they were hired! They got their interviews on the basis of my letters and their research statements, and got the jobs because they are great scientists who had done outstanding, as of yet unpublished, work. If anything demonstrates the fallacy of the glamour mag or bust mentality this is it.

In fact, as a co-founder of PLOS and a strong, vocal advocate of open science his group primarily publishes in PLOS journals.  He hasn't been the last author on a non-PLOS paper since a PNAs paper in 1998, so he is certainly putting his science where his mouth is. Earlier in the day, William Gunn (@mrgunn) made a similar argument:

I'm starting to think that the plodding careerists who always raise the "but I have to publish in X journal for my career" criticism just need to be routed around. You shouldn't be in science because you want a stable career, you should be here because you can't fathom doing anything else.

Now these are both admirable positions to take.  But as the title alludes to, this is a chicken and egg problem.  If a postdoc decides to only publish in open access journals then he hopes that prospective departments and grant committees agree with his stance.  If a faculty member takes this stance he hopes that grants and tenure/promotion committees agree.  If tenure and promotion committees agree, then they hope granting agencies agree.  If granting agencies agree then they hope that the public (or their foundations or government agencies agree).  If any link breaks, then its a risk.  As someone who agrees with this, I might find a department happy with this policy, but if my NIH study section isn't on board then I am in some trouble.

Taking this further, I thought why should this even only apply to open access and open review.  Lets say I do all my research totally in the open, self-publishing it online either on my own site or on a pre-print server like ArXiv or the newer Faculty of 1000 Research and engaging in discussion on these forums.  If I completely ignored journals entirely, would anyone accept this as being ok?  I posted it on twitter, and there were positive responses, but that is really hard to imagine.

Without anonymous peer-review how could I (or the reader) be assured that controls were done properly and the context of the work was appropriately stated.  If that is done via peer review posted with the article anonymously how could the reader be sure I didn't just delete the bad reviews or comments.  If I post some data on a blog or pre-print server and some other person finds it, expands on it and publishes it in Science then do I have any right to feel aggrieved?  Who should get the credit?

In an ideal world, things might work analogously to how Rosie Redfield (@rosieredfield) has addressed the arsenic life question.  After posting an initial rebuttal online, Dr. Redfield did some experiments, engaged with the community about the data and put it all together.  This was (to me at least) the first archetypical evidence of the open evaluation of a research claim.  It was done in the open, public suggestions were incorporated, the work was posted to a preprint archive and then in the end.... it was submitted to Science.

Now this is not entirely fair to Dr. Redfield, Science was chosen as that was where the first arsenic paper was published and where her (and other) critiques were published.  But if this, most open and public scientific re-evaluation, still needs glamour mag validation what hope does the rest of research have?

So who should mandate this?  Various policies of public access have helped make publicly funded research open access and a new generation of scientists has shown more proclivity towards goal but who needs to take the first steps.  Dr. Eisen suggests it has to be everyone.  For this change to happen, primary researchers, group leaders, departments, granting agencies and the public all need to take that step, and leave those who are betrothed to impact factor chasing looking like relics of the past.

Creative Commons License
Chickens and Eggs by Dave Bridges is licensed under a Creative Commons Attribution 3.0 Unported License.

Saturday, April 16, 2011

PI(3)P and Exocytosis

ResearchBlogging.org

The classic opinion regarding PI(3)P’s role in intracellular trafficking is that it is synthesized and functions primarily on early endosomes. Several recent publications have highlighted a potential second role for this lipid in exocytosis. Extending previous work by this group and others on the positive role of PI3K-C2a in neurosecretory pathways (1,2) and GLUT4 exoctyosis (3,4) this paper from Tania Maffucci's group interrogates the role of this lipid kinase in insulin secretion in INS1 cells. Combined these results suggest a general role for PI3K-C2a and its product, PI(3)P in exocytotic events.

This group has been investigating the role of the class II PI3K isoforms in exocytosis in a variety of systems. In this paper they investigate the role of PI3K-C2a in insulin secretion using INS1 rat insulinoma cells as a model. Stable knockdown cells did not show any defects in proliferation, calcium signaling, intracellular insulin levels or the expression levels and sub-cellular localization of exocytotic proteins. The PI3K-C2a knockdown cells did however show significant defects in insulin secretion, stimulated by either a secretagogue cocktail or potassium chloride.

Mechanistically, the authors show that there is no defect in insulin granules proximal to the plasma membrane at the resting state. They do detect a decrease in the amount of SNAP25 hydrolysis induced by the secretagogue cocktail. SNAP25 hydrolysis has been proposed to be an important step in the fusion of exocytic vesicles (5). This proteolytic event has not been established as a major mechanism in exocytosis, and it may only correlate with defects in PI3K-C2a signaling. However if reduced SNAP25 proteolysis is the mechanistic defect resulting from PI3K-C2a knockdown, then this suggests a role in protease regulation by PI(3)P or another PI(3)P-derived molecule as a key part of the general exocytotic machinery. It is also possible that there is another, as of yet unstudied role of PI3K-C2a and PI(3)P in exocytosis.



Dominguez, V., Raimondi, C., Somanath, S., Bugliani, M., Loder, M., Edling, C., Divecha, N., da Silva-Xavier, G., Marselli, L., Persaud, S., Turner, M., Rutter, G., Marchetti, P., Falasca, M., & Maffucci, T. (2010). Class II Phosphoinositide 3-Kinase Regulates Exocytosis of Insulin Granules in Pancreatic Cells Journal of Biological Chemistry, 286 (6), 4216-4225 DOI: 10.1074/jbc.M110.200295

References


(1) Meunier, Frederic, Shona Osborne, Gerald Hammond, Frank Cooke, Peter Parker, Jan Domin, and Giampietro Schiavo. “Phosphatidylinositol 3-Kinase C2{alpha} Is Essential for ATP-dependent Priming of Neurosecretory Granule Exocytosis.” Molecular Biology of the Cell 16, no. 10 (2005): 4841-4851. PubMed, DOI.

(2) Wen, Peter J, Shona L Osborne, Isabel C Morrow, Robert G Parton, Jan Domin, and Frederic A Meunier. “Ca2+-regulated pool of phosphatidylinositol-3-phosphate produced by phosphatidylinositol 3-kinase C2alpha on neurosecretory vesicles.” Molecular biology of the cell 19, no. 12 (December 2008): 5593-603. PMC, PubMed, DOI.

(3) Maffucci, Tania, Anna Brancaccio, Enza Piccolo, Robert C Stein, and Marco Falasca. “Insulin induces phosphatidylinositol-3-phosphate formation through TC10 activation.” The EMBO journal 22, no. 16 (August 15, 2003): 4178-89. PubMed, DOI.

(4) Falasca, Marco, William E Hughes, Veronica Dominguez, Gianluca Sala, Florentia Fostira, Michelle Q Fang, Rosanna Cazzolli, Peter R Shepherd, David E James, and Tania Maffucci. “The role of phosphoinositide 3-kinase C2alpha in insulin signaling.” The Journal of biological chemistry 282, no. 38 (September 21, 2007): 28226-36. PubMed, DOI.