Papers to read???

[rexzeppelin]

So, now that I'm officially done with the application/interview process, I'd like to completely whitewash the portion of my brain that I devoted to this endeavor (entirely too large I fear) and get back to what interested me in a PhD in the first place.

 

To that end, has anyone read any interesting papers/reviews recently they would recommend?

[Raerosk]

I've gone through and started reading more specific papers for my potential PIs, and looking for other people that might be interesting. May be worth a go!

[bsharpe269]

What area of biophysics are you interested in?

[biotechie]

So, now that I'm officially done with the application/interview process, I'd like to completely whitewash the portion of my brain that I devoted to this endeavor (entirely too large I fear) and get back to what interested me in a PhD in the first place.

 

To that end, has anyone read any interesting papers/reviews recently they would recommend?

 

Read up on the CRISPR/Cas9 system. Even though it is so new, I've literally been tested on it in every class as a first year this year. I'm sure next year will be no different! It would be especially helpful for you to learn about the structural stuff and the different uses for the different versions of Cas9. There's the normal version (with nickase and nuclease, really good for knockout and some recombination), nickase only version (nicks a single strand, useful for things like recombination), and a mutant that is nickase and nuclease deficient (think promoter "tiling" with lots of guide RNAs to block gene expression).

There's also some really crazy stuff going on with iPS cells, which are also going to be something you're going to be encountering in classes, too, most likely. There are some cool new papers out on iPS cells and differentiation into heart cells and how some of these cells need to be altered mechanically.

 

My favorite things to read about are novel gene regulation and knockout systems and nearly anything epigenetics. I also like looking at seemingly normal epigenetic abnormalities and seeing how those contribute to autoimmunity. You'd be surprised how much you can find simply by reading and data-mining. There's so much whole-genome bisulfite sequencing done, now, as well as lots of histone ChIP. There are also lots of mechanistic studies involving chromatin structure and specific conformations of proteins that a biophysicist might like.

 

If none of those sound cool, you could always stalk your potential PIs' publications and get ahead of the game! Feel free to message me if you have questions or want more specific titles. I don't know much on the heart stuff as I learned about it in a seminar, but the rest.... I could discuss in detail.

[threading_the_neidl]

I agree with biotechie. CRISPR's going to be huge, read up on it now, it's already showing up everywhere. All I know about iPS right now is the paper with almost certainly faked data that may or may not be retracted soon, showing that putting acid on cells will reprogram them to an iPS state. You could read that one and all the hilarious online follow ups for funsies.

[aberrant]

Read up on the CRISPR/Cas9 system. Even though it is so new, I've literally been tested on it in every class as a first year this year. I'm sure next year will be no different! It would be especially helpful for you to learn about the structural stuff and the different uses for the different versions of Cas9. There's the normal version (with nickase and nuclease, really good for knockout and some recombination), nickase only version (nicks a single strand, useful for things like recombination), and a mutant that is nickase and nuclease deficient (think promoter "tiling" with lots of guide RNAs to block gene expression).

 

1. The "normal version" is a nuclease with HNH and RuvC domains that can cut (+)- and (-)- DNA strand individually to generate DSB in DNA. Anything else (i.e. single-point mutated nickase from SpyCas9 D10A or double-mutated nickase) are for either gene modification (using 2 gRNA, single-point mutated nickase, and HR / NHEJ to repair) or transcription regulations (using double-mutant SpyCas9 and a gRNA).

 

2. While it may seems to be new, the first thorough in vitro study published in 2012 on Science by Jinek et al. Then in 2013 there are +50 papers predominantly on its application in vivo. February of 2014 is the time when the structure of apo and holo form of Cas9 are published. In terms of application, OP may want to know the pros and cons between using Cas9, TALEN, and ZFN.

 

ps. especially the reason why people use nickase / single-point mutated SpyCas9 for genome engineering as opposed to the wildtype.

 

 

I agree with biotechie. CRISPR's going to be huge, read up on it now, it's already showing up everywhere. 

 

Application of CRISPR-Cas9 = yes. Otherwise, if you are just talking about CRISPR per se, then the biological question (up next) is how the immune system acquire spacers into the host genome and generate an array.

 

 

End for your research ethics class and whatnot: Stem-cell method faces fresh questions

http://www.nature.com/news/stem-cell-method-faces-fresh-questions-1.14895?WT.ec_id=NATURE-20140320

Edited March 22, 2014 by aberrant

[Eigen]

Biophysics is a bit outside my area to give specific recommendations, but here are two more general ones:

 

1) Read papers by your PI. And your PI's PI. And other potential committee members. 

 

2) Pick a couple of journals that are consistent cornerstones of your field. Subscribe to ASAP e-mail alerts (most support this or an RSS-type feed). Spend a bit of time each morning catching up. 

 

1 really helps ground you in the immediate work you're likely to be doing, while 2 gives you a good, consistent look at what's hot/trending in your field/subfield. 

 

I don't get as much time to read the literature as I'd like, but I used to keep up with 5 or 6 major journals my first few years, and it held me in really good stead. 

[Monochrome Spring]

I second what Eigen said. I recommend reading through your PI's papers, as well as the papers of other faculty at your university who may be doing research that you are interested in. I think it will give you a big head start to be able to discuss the previous research of numerous faculty members in your program, and it could help you with picking out committee members.

 

In addition to reading through the recent papers in the major journals in your field, I recommend going through your old undergrad (or masters) materials, and seeing which papers were cited frequently. Read through those again, because they are the foundation of your field and future work; being able to pull them up in conversations will also help.

 

I personally love reading through major review papers. Email your PI and maybe other professors who you've talked with, and ask if they can send you a few of their favorites. And you can always piggyback off of references in these, as well.

[biotechie]

1. The "normal version" is a nuclease with HNH and RuvC domains that can cut (+)- and (-)- DNA strand individually to generate DSB in DNA. Anything else (i.e. single-point mutated nickase from SpyCas9 D10A or double-mutated nickase) are for either gene modification (using 2 gRNA, single-point mutated nickase, and HR / NHEJ to repair) or transcription regulations (using double-mutant SpyCas9 and a gRNA).

 

2. While it may seems to be new, the first thorough in vitro study published in 2012 on Science by Jinek et al. Then in 2013 there are +50 papers predominantly on its application in vivo. February of 2014 is the time when the structure of apo and holo form of Cas9 are published. In terms of application, OP may want to know the pros and cons between using Cas9, TALEN, and ZFN.

 

ps. especially the reason why people use nickase / single-point mutated SpyCas9 for genome engineering as opposed to the wildtype.

I really need to stop trying to type things when I'm so tired, though in the whole grand scheme of things, CRISPR is still pretty new. The new paper on the structure and use of the use of different Cas9 mutants was what I was trying to get at. I'm fairly certain we were hit so hard with the CRISPR stuff in classes this year was simply because that's when it exploded. We weren't really questioned about what the original function of it was, but more application and how methodology differs between Cas9 and slightly older systems. It is also a really fun system to work with, and in ways is simpler (such as you always use the same Cas9, just new guides rather than having to make a new TALEN), but alternately, you can have a loss of specificity with off-target effects that you can mostly get rid of with other methods like TALENs. I've used both TALEN and Cas9 (currently working with D10 mutant), and I like both for different applications.

To add to what Mono said: Reviews are great to get a general understanding of a subject, but make sure that you actually dig deep and pull out the relevant sources when you're writing up things for grants publications in the future. The last thing you want is for your grant to not be funded or your paper not accepted because one of the reviewers happens to be the guy who discovered something you're basing your research off of and you neglected to cite them!

 

Since you're going to be doing a lot of reading to help you solidify what you know and need to know, it might be good to also start working with a citation manager to figure out which one you like, learn how you want to organize, and start annotating things that you think will be important. Nothing sucks more than knowing a certain paper is important and then when you go to write your document, you can't remember why you thought it was important! I love Mendeley, but other people like Zotero. Both of these are free and you can take citations and export them in an Endnote format if that's what your future PI wants you to use.

 

What I like to do is read a couple of reviews to learn about something, and then I dump those into a review folder in Mendeley. Anything I needed from the review, I try to find the original source, and that goes into a folder that I actually pull citations out of for publication. I don't find myself citing the reviews often, but occasionally, when they suggest new interaction schemes, I will cite them.

[Eigen]

Oh, here's my other, major, suggestion for starting to read papers:

 

Get a citation manager. Use it. 

 

By the time I realized I needed one, I already had ~150 PDFs in folders to go back and organize. It would have been much easier to have been organizing them and annotating them from the beginning!

[ERR_Alpha]

Oh, here's my other, major, suggestion for starting to read papers:

Get a citation manager. Use it.

By the time I realized I needed one, I already had ~150 PDFs in folders to go back and organize. It would have been much easier to have been organizing them and annotating them from the beginning!

I recommend Zotero if you use Firefox. Although it doesn't seem to work well with any other browser.

[persimmony]

Oh, here's my other, major, suggestion for starting to read papers:

 

Get a citation manager. Use it. 

 

By the time I realized I needed one, I already had ~150 PDFs in folders to go back and organize. It would have been much easier to have been organizing them and annotating them from the beginning!

 

Which one do you use?

[Eigen]

I use Endnote, but that's largely just because it was what my department had available for free. 

 

I do like it though, even if I'm about 5 versions out of date. 

 

IMO, what you choose doesn't matter hugely, as you can pretty easily import/export libraries between most of the main ones. So using whatever you have easy access to gets your library started, and you can swap down the line. 

[biotechie]

I use Endnote, but that's largely just because it was what my department had available for free. 

 

I do like it though, even if I'm about 5 versions out of date. 

 

IMO, what you choose doesn't matter hugely, as you can pretty easily import/export libraries between most of the main ones. So using whatever you have easy access to gets your library started, and you can swap down the line. 

 

It really is pretty easy to switch. I would probably start with one of the free ones like Mendeley or Zotero since you can always export at least your citations from those into a format usable by Endnote. I use Mendeley and I love it for annotating things; it is the citation manager I used for my masters thesis. My new PI uses Endnote, so I can export the citations I have from Mendeley to Endnote when I need to write a paper with him.

 

I... don't get along with Zotero, but I have no idea why, so I can't pass judgement. Mendeley gets along with Safari and Firefox from my experience. I currently use the online storage to sync my papers between my school and home computers, but I don't know what I will do when I hit the maximum amount I'm allowed to store!

Edited March 26, 2014 by biotechie

[ERR_Alpha]

Maybe I will try Mendeley. Is it free? I'm now a safari user so it's frustrating to go back to Firefox just to cite things.

[Eigen]

Honestly, the not-online part is what I like about Endnote. I didn't want to have my reference manager be browser based. 

 

One other you might give a try is the free Reference Manager from the American Chemical Society- ChemWorx. While made by the ACS, it's not chemistry specific, and is pretty decent and improving rapidly. 

 

Alternately, on a Mac, I hear a lot of people who like Papers. 

[devneuro18]

I would definitely recommend Papers, it's a great way to organize any papers that you have. I've head the iPad and iPhone apps are pretty great too. You can also highlight and take notes within the papers, so it's mostly meant as an archive. I have no direct experience with the Windows app, but it does exist.

 

It also has a citation tool built in that works similarly to Endnote, but my institution has an Endnote license and Papers makes it easy to export your library to Endnote for citation purposes. I find that Endnote handles citations better, for example if you downloaded a paper while it was an early/web release, Endnote is smart enough to find the journal/page specific information that you need when citing it.

[biotechie]

Honestly, the not-online part is what I like about Endnote. I didn't want to have my reference manager be browser based. 

 

One other you might give a try is the free Reference Manager from the American Chemical Society- ChemWorx. While made by the ACS, it's not chemistry specific, and is pretty decent and improving rapidly. 

 

Alternately, on a Mac, I hear a lot of people who like Papers. 

 

I actually use a desktop application for Mendeley. I think it was originally browser based when it started up, but now is a desktop application. I only use the internet part to sync my notes between my computers. However, I just figured out today that I can do it on my external hard drive the same way, so I no longer even need the internet or my browser and I don't have to worry about running over my online "space." You're not screwed out of reading, citing, and annotating your papers when you're offline since you can have it store your papers in a specific place for you on your hard drive.

 

The browser compatibility thing I was talking about was for the add-on that will pull the citation in for you. You don't even really need that if you have the DOI or PMID. Even if you only have the title + an author or two, you can get it to find the info. Endnote does have Mendeley beat, there, but I haven't had any issues.

 

I like Papers, too, but I don't use it for my academic reading. I actually use it for my creative writing stuff.

 

Yes, ERR_Alpha, it is free:

www.mendeley.com

 

And while I'm posting links, here's Zotero, which is also free:

https://www.zotero.org

 

You guys can look at the sites for yourselves to see what will and will not work for you since it is going to vary a ton. I would just try to get something free to start that will play nice with EndNote as it seems to be what the majority of people are using.