Sometimes the good guys win

(by drugmonkey) Sep 30 2014

I've mentioned a time or two that I think the DREADD approach is infinitely more useful than optogenetics for anything that matters.

So congrats to the team for this new award.

DREADD2.0: AN ENHANCED CHEMOGENETIC TOOLKIT

DESCRIPTION (provided by applicant): The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has the ambitious goal of elucidating how neuronal ensembles interactively encode higher brain processes. To accomplish this goal, new and improved methods for both recording and manipulating neuronal activity will be needed. In this application, we focus on technologies for manipulating neuronal activity. The major significance of this application is that we will provide an enhanced chemogenetic toolbox that allows non-invasive, multiplexed spatiotemporal control of neuronal activity in domains ranging from single synapses to ensembles of neurons. To achieve this, we will provide: Chemical actuators with improved pharmacokinetics and pharmacodyamics suited for use with current DREADDs in eukaryotes ranging from Drosophila to primates (Specific Aim #1) Photo-caged CNO and other chemical actuators to provide millisecond-scale control (Specific Aim #1) Novel DREADDs and 'split-DREADDs' targeted to distinct neuronal pathways to enable multiplexed interrogation of neuronal circuits (Specific Aims #2 and 3) Chemogenetic platforms with minimized desensitization and down-regulation (Specific Aim #3)

I am excited to see where this leads.

More awards under The BRAIN Initiative.

12 responses so far

The new ASBMB President has words for the science riff-raff

(by drugmonkey) Sep 29 2014

Now honestly, this thing reads like a spoof or some top-quality trolling akin to my Boomer bashing. Albeit without a shred of actual data on which it is based (unlike my Boomer bashing).

However, you will be interested to hear the new ASBMB President's analysis of the real problem in science today.

Two or three decades ago, this system was effective, yet I now judge it to be flawed. What went wrong? I submit that the demise of the review process can be attributed to two changes. First, the quality of scientists participating in CSR study sections two to three decades ago was, on average, superior to the quality of study section participants today. Second, study sections have become highly specialized such that they narrowly define a differentiated club of biomedical research.

Hrm, hrm, I submit to you, hrm hrm, that I and my fellow Great Men of Science used to get our grants funded every time we submitted them. Now things have changed! Clearly there is a problem that is simple to diagnose. Read on.

Among all problems leading to devolution of CSR study sections, the elephantine expansion of the biomedical research complex tops the list. Biomedical research in the 1960s and 1970s was a spartan game.

Wait, what? Does this guy know it is 2014? That would make it three to four decades ago...but who is counting.

First, the average scientist today is not of the quality of our predecessors; it’s a bit analogous to the so-called “greatest generation” of men and women of the United States who fought off fascism in World War II compared with their baby boomer children. Biomedical research is a huge enterprise now; it attracts riff-raff who never would have survived as scientists in the 1960s and 1970s. There is no doubt that highly capable scientists currently participate in the grant-review process. Likewise, unfortunately, study sections are undoubtedly contaminated by riff-raff.

Hmmmm. Okay so let me just think about this. The greatest change in the population of Professor-scientists since the 1070s is....hmmm. Women? Persons underrepresented in the sciences (and academia)? Those from a less-well-off background? All of the bloody above?

Good LORD what a snob.

A second cause of the demise in study section quality can be attributed to the fact that it is a thankless task balanced by few benefits. Three to four decades ago, it was a feather in one’s cap to be appointed to an NIH study section. When I joined the molecular cytology study section in the 1980s, Bruce Alberts was chairman, and the committee included the likes of Tom Pollard and all kinds of superb scientists. To spend three meetings per year with an esteemed group of scientists was both inspirational to me as a young scientist and of tangible value to my maturation as a researcher.

Less than one decade ago I went on study section and it was considered by all of my local peers (and members of my field external to my University) to be quite a feather in my cap. I also had the opportunity to spend three meetings a year with an esteemed group of scientists in my field. It was inspirational to me and of tangible value to my maturation as a scientist.

Wow. It is almost like nothing has changed.

Finally, as study sections have become ever more dedicated to thin slices of the biomedical landscape, participants are exposed to less and less science outside of the narrowly defined disciplines covered by their individual study sections. As such, one rarely learns much of anything new by participating in an NIH study section meeting.

I can't speak to every study section but I did have the good fortune to be appointed to one with a broad mission. Broad across IC assigned for possible funding, broad in study subject population / models and broad in scientific questions being asked. From my perspective, of course. Not sure how Dr. McKnight would see it but I'm willing to argue the merits of that study section on the stats.

let’s consider what might be expected from a grant review committee composed largely of second-tier scientists with limited knowledge of the breadth of biology and medicine. I propose that these committees are equally good at ensuring that the worst and best applications never get funded. They can see a terrible grant wherein the science is flawed and the investigator has no track record of achievement. These committees are, unfortunately, equally good at spotting and excluding the most creative proposals – the grant applications coming from inspired scientists whose research is damned because it is several steps ahead of the curve and damned because it comes from an applicant not blessed with club membership.

as they say on Wikipedia, [citation needed].

Now, to the second of two evils: the evolution of scientific clubs. Back when we used to “walk miles to school,” the scientific meetings we attended had some level of breadth.

Ok. If this is an intentional troll, this is the tell right here. Right? Right?

Fast-forward 30 years, and what do we now have? The typical modern biomedical meeting spends a week on a ridiculously thin slice of biology. There are entire meetings devoted to the hypoxic response pathway, sirtuin proteins, P53, mTor or NFkB. If a scientist studies some aspect of any of these domains, he or she absolutely has to attend these mindless meetings where, at most, some miniscule increment of advancement is all to be learned.

Is it possible that science really has gotten more complex so that low hanging fruit cannot be scooped up by a generalist, gentleman dilettante anymore? I mean, it couldn't be that, could it?

Damn the fool who does not attend these meetings: The consequence is failure to maintain club membership. And why is club membership of such vital importance? Yes, precisely, there is nearly a one-to-one correspondence between these clubs and CSR study sections.

Actually, the study section I spent the most time reviewing for contained LOTS of people that tend to attend meetings that I do not attend. I met many of them for the first time on study section. So the "one-to-one correspondence" simply doesn't square with my experience. Oh, and btw, I have ad-hoc'd on panels that are related but have a more defined focus than the one I served as an appointed member. Guess what? Also a dearth of "one-to-one correspondence" with any particular scientific meetings I or they attend.

So, to wrap up, this guy has zero data for his assertions, they come from the expected direction of unearned privilege of those who got their starts in the 1960s and early 1970s and his claims about modern study section are at considerable odds with my own experiences.

I will be fascinated to see if my readers share his view on the modern study section experience.

ETA: A check of Dr. McKnight's funded grants from the NIH suggests he is no stranger to the Special Emphasis Panel.
__
h/t: Some twitter troll who shall not be identified unless s/he so choses.

60 responses so far

Question of the Day

(by drugmonkey) Sep 29 2014

The NIH funds grants at "foreign applicant institutions", meaning a University in another country.

In these times should we be continuing this practice or is scientific grant protectionism a good idea?

29 responses so far

Boomer academics plan to never, ever retire

(by drugmonkey) Sep 26 2014

Somehow I missed this in the Inside Higher Ed a year ago.

Some 74 percent of professors aged 49-67 plan to delay retirement past age 65 or never retire at all, according to a new Fidelity Investments study of higher education faculty. While 69 percent of those surveyed cited financial concerns, an even higher percentage of professors said love of their careers factored into their decision.
...
For the faculty boomers who will delay retirement due to professional reasons, 89 percent want to stay busy and productive, 64 percent say they love their work too much to give it up, and 41 percent are unwilling to relinquish continued access to – and affiliation with – their institution.

USBirthsIn related news, this chart tells you about the size of the Boomer, X and Millennial generations in the US. Hint, look at the total-births trace. This has very real consequences. We see the effects of the Boomers in many job sectors, of course, but the academic science one is a job sector which encourages the hardening of generational privilege. People do not become too physically worn out to work. They clearly want nothing other than to die as an active member of the workforce. They simply persist.

At present, the oldsters/Boomers are a huge part of the distribution of the Professor class.

They have a disproportional and distorting effect on everything.

When they DO finally die off then the replacement will come from the Millennial generation. So big ups there, o complaining millennials! The future is bright.

Sourced from the CDC.

h/t: Neurorumblr

75 responses so far

Ask the DM Blog Braintrust: Advice on First Study Section?

(by drugmonkey) Sep 24 2014

A query came it that is best answered by the commentariat before I start stamping around scaring the fish.

I'm a "newbie" heading to study section as an ESR quite soon...
I'd really, really appreciated it if you could do a post on

a) your advice on what to expect and how to ... not put my foot in my mouth

b) what in an ideal world you'd like newbies to achieve as SS members

Thoughts?

32 responses so far

Poll of the day

(by drugmonkey) Sep 24 2014

If some throwaway sentence in the Aims page draft I'm looking over for PhysioProffe stimulates my curiosity about a cool model then he is obligated to throw a least a postdoc year at the topic, correct?

10 responses so far

Federal RePORTER!!!!!!!!!!!!!!!!!!

(by drugmonkey) Sep 24 2014

This is soooo friggin cool.

There is now a tool to search all Federal research grants, i.e. across the various funding agencies.

Federal RePORTER awaits!

13 responses so far

On Twitter/blog handles and the inferiority complex of Penn

(by drugmonkey) Sep 24 2014

APS has a News bit on a new paper.

People and institutions who are marginal members of a high-status or well-esteemed group tend to emphasize their group membership more than those who are squarely entrenched members of the group, according to new research published in Psychological Science,

The full cite:
Rozin P, Scott SE, Zickgraf HF, Ahn F, Jiang H. Asymmetrical Social Mach Bands: Exaggeration of Social Identities on the More Esteemed Side of Group Borders. Psychol Sci. 2014 Aug 20. pii: 0956797614545131. [Epub ahead of print] [PubMed, Publisher]

A few key results:

Universities at the border of the university category emphasized their university identity more than archetypal universities did. On average, master’s universities used the word university in 62.2% of self-references (SD = 31.6%, n = 151), whereas the corresponding mean for national universities was 46.4% (SD = 31.0%, n = 55), t(204) = 3.19, p = .002, 95% confidence interval (CI) for the difference = [6.0%, 25.5%], d = 0.50.

and

Small (n = 34) airports were more likely to emphasize their status as an international airport than large airports were (n = 20). On average, small airports used the word international in 68.2% (SD = 30.3%) of self-references, whereas the corresponding mean for large airports was 31.4% (SD = 29.1%), t(52) = 4.38, p < .001, 95% CI for the difference = [20.0%, 53.8%], d = 1.24.

and

Penn students were more likely to mention “Ivy League” or “Ivy” in describing their university than Harvard students were, but directing individuals to answer in a public context, if anything, decreased “Ivy” mentions. In the public condition, none of 30 Harvard students mentioned “Ivy,” whereas 9 of 33 Penn students (27.3%) did. In the private condition, 4 of 24 Harvard students (16.7%) mentioned “Ivy,” whereas 7 of 20 Penn students (35%) did.

I was recently expressing how dealing with the local public school system was the one place in my nonprofessional life that induced me to deploy my doctoral credentials. Part of this is by seeing how consistently the public school people use "Doctor" for anyone in their system who happens to have obtained a doctoral degree. I guess I know a little more about why those people do that.

Ever since joining social media I've been bemusedly struck by those people who choose to put "Doctor" or "PhD" or even "Professor" in their handles and blog titles- whether they go by a pseudonym or not. Now, of course, I am thinking about whether they were in a boundary condition when they came up with those identifiers.

It also makes me think about women and minorities in the sciences. Do people flagrantly underrepresented in a profession feel permanently on the group border? Does this influence their deployment of their credentials?

Those of us who do not feel as though we are on the border, and have a sort of lazy, comfortable ambivalence to deploying our credentials, should probably think about this a little more.

__
h/t: @amyjccuddy

40 responses so far

Chin up, grantseekers!

(by drugmonkey) Sep 22 2014

I'm in the middle of a slightly unusual grant reviewing task. It's weird in several ways but all you need to know is that all of the proposals were previously scored VERY highly. As in highly enough to get funded, highly.

 

You might imagine that these proposals would all be kick ass wonders of grant preparation, supportive preliminary data, innovation, slick and seamless plans of attack and all that jazz.

 

If you have been paying attention to my continued assertions about what happens in regular study section you will not be surprised in the least to learn that this is not so.

 

These suckers have warts all over them. Some of them, in my view as just one reviewer, are pretty terrible on many of the usual dimensions.

 

Just goes to show you.

36 responses so far

Your Grant in Review: Longitudinal Human Studies

(by drugmonkey) Sep 22 2014

Man.

Reviewing a competing continuation of a longitudinal human subjects study always has a little bit of a whiff of extortion to it. I'm not saying this is intentional but......

 

The sunk cost fallacy is a monster.

3 responses so far

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