Monday, January 27, 2014

Five Short Facts About Fat Cell Biology

Cell recently posted a huge review of fat and adipose biology written by Evan Rosen and Bruce Spiegelman.

There are currently three types of fat known: white, brown, and beige.  If you're interested in where fat tissue comes from and how it behaves, skip ahead to the section titled "The Developmental Origins of Adipose Tissue: A Bloody Mess", which means that it's actually bloody and that it's just bloody confusing to understand how all the genes involved relate to each other.  There you'll find a handful of good factoids:
  • The total number of fat cells humans carry as adults is set by adolescence.
  • Humans turn over about 8% of their fat cells per year.
  • Mice turn over about 0.6% of their fat cells every day.
  • Fat cells can be derived from stem cells that can also create blood cells.
  • Brown fat cells are derived from stem cells that actually reside in muscles, not fatty tissue.  A single gene controls the switch between the two.
Besides giving you the 50,000 ft view of fat biology, another key take-home message in this review is that having basic stakes in the ground to frame research questions is a necessary catalyst before triggering a lot of research down the road.  This may be obvious, but it's worth repeating when good examples arise.

In this review, it's best shown in the first figure, where it's not until several fat related cytokines were identified in the mid-1990's that work in the fat field really took off.  Though interest in the field slowly grew, it wasn't until reaching milestones like the discovery of leptin and adiponectin that both raw and relative numbers of papers (blue and red), respectively, shot up from a baseline that spanned more than two decades.

Monday, January 20, 2014

Franklin's List: Helping Scientists Become Politicians

GEN has an excellent and timely article on an emerging political group, Franklin's List, that's helping scientists get involved in politics in the United States, by directly helping them become politicians.  Though the group is new, they already acknowledge several obstacles that need to be paid attention to. The largest once are human issues and have little to do with a need for money:
One key roadblock those recruits, and Franklin’s List, will need to surmount is cultural: Until lately, investigators and other STEM professionals have balked at going into politics. [Shane] Trimmer (Franklin's List Executive Director) says that’s starting to change following years of flat or reduced spending on NIH. ... “They’re seeing how the decisions made in Congress by politicians are directly affecting their ability to do research. Now they’re seeing that if they do not get more involved, then these things will just keep on happening,” he added.
It's almost as if that imaginary world of scientists cloistered in their labs ignoring reality is real, and represents a major liability to the research enterprise.  You just can't get tenure and skive off from the rest of the world to do research until your retirement at the age of 79.

The whole idea of scientists forming a lobby group reminds me of a conversation I had with another trainee long ago at a Stem Cell Network conference.  He was a postdoc and I was a PhD student, and he took the position that that scientists, being paid to manage government funds, couldn't use those same government funds to lobby the government for more money.

I argued that that wasn't true; once grant money was paid to people (researchers, technicians, students, etc.), they could do whatever they wanted.  That included spending it on professional bodies that, like those for teachers and physicians, spend a lot of time and energy on negotiating better terms for their members.  Why scientists aren't very good at doing this puzzles me to this day.

But Franklin's List seems like it can partly fill this need for a scientific lobby group, at least in the United States.  Interestingly, it looks like it'll focus on gathering scientists at local levels to try and grow out candidates for higher political levels.  Kind of like running farm teams.
“The STEM candidates we’ll be searching for who have been in the lab or in academic circles, their idea was always to be in academia as a biologist or a physicist. They don’t have the network that somebody might have who has been a businessperson or an attorney in the community and might always have, in the back of their mind, thought about politics as an option,” Trimmer said. “It will be much easier for them to work their way up and to build that grassroots support.”
The GEN article is worth the few minutes to read, and it definitely portrays Franklin's List as a movement to watch.

Tuesday, January 14, 2014

Stunning Protein Animations by Nanobotmodels Studio

Yuriy Svidinenko, head of Nanobotmodels, is running a crowdfunding campaign to produce more jaw-dropping animations like this one of nanoparticles delivering drugs to cancer cells:

He's proposing to use the crowdfunding proceeds to produce an animated video about cancer biology and proteins involved in the process, and his IndieGoGo pitch video can be seen below.

You have to wait to see the cool renderings of human IgG at 1:00, what appears to be a protein encapsulated in a lipid nanoparticle at 1:12, and a translucent cell (a neuron?) starting at 1:38.

Apparently rendering costs are a significant fraction of making these videos (~40%), which he estimates at about $65-85 per secondThe campaign runs until February 25th, 2014.

Best of luck Yuriy!

Friday, January 10, 2014

Science Transforms War, Transforming Science

At Nature, David Kaiser, an MIT Professor and Head of the Program in Science, Technology, and Society, writes about how the Second World War's need for physicists to run huge research programs transformed the model of science:
Until the war, most scientific research in the United States had been supported by private foundations, local industries and undergraduate tuition fees. After the war, scientists experienced a continuity — even an expansion — of the wartime funding model. Almost all support for basic, unclassified research (as well as for mission-oriented defense projects) came from the federal government.
While the main point here is that government became the major funder of research, the point that's more important to remember is Kaiser's description of research, pre-WW2, as being paid for by (and probably driven by) foundations, industry, and tuition. 

But in the context of changing government funding, these are the same sources of money that seem to be becoming more and more important today.  Could it be that the model of running science for the last 60 to 70 years has been 'abnormal'?

Part way through, Kaiser throws in another interesting historical quip:
Veterans of the intense, multidisciplinary wartime projects came to speak of a new type of scientist. They touted the war-forged 'radar philosophy' and the quintessential 'Los Alamos man': a pragmatist who could collaborate with everyone (emphasis is mine) from ballistics experts to metallurgists, and who had a gut feeling for the relevant phenomena without getting lost in philosophical niceties.
Learning to work in collaborations and to do collaborative science is probably one of the more important and useful skills to pick up during a PhD, and it seems like the idea of a pragmatic 'serial collaborator' who manages to identify common ground with others in other disciplines seems to have also originated in the post-war period.

Thursday, January 9, 2014

Frozen Human Brains, Stem Cells, and Ice Cream

Signals just posted a short summary I wrote on this paper, where a team at Columbia University and the New York Stem Cell Foundation managed to create iPS cells from human brain tissue that was frozen for 11 years. 

The paper itself is actually a neat example that human cells are pretty resilient, as the team specifically used tissue samples that weren't protected against freezing with glycerol or DMSO, common additives to prevent ice crystals from forming and damaging the cells.

And since stem cells were created from patients with four different neurological diseases, it also means that other kinds of poorly stored samples, not protected with an antifreeze, might be used to make model cells as well. 

Since Signals has the summary of the paper, I'll digress on the topic of antifreezes here.  You might also know that antifreezes aren't just useful for storing biological samples in freezers; many organisms protect themselves from freezing with antifreeze compounds or antifreeze proteins in their own bodies.  

Several antifreeze protein structures.  From RCSB.

Besides keeping organisms alive, antifreeze proteins also have a variety of useful applications for humans (which obviously don't have any), with the best one I know of is the use of fish antifreeze protein as an additive to ice cream.

I first heard of this in a talk by Peter Davies, a scientist at Queen's University, who described how antifreeze proteins were identified in mealworms. He describes some of that work in this short interview at NPR, where he also adds that the proteins were quickly rebranded by companies using the proteins in food:
DAVIES: Unilever, which is a big company in Europe, who make frozen foods like ice cream for example, they have for some time now been putting the antifreeze proteins into especially low-fat ice cream. Now they don't call them antifreeze proteins because the public would, the consumers would be perhaps nervous about the idea of antifreeze being in food. So they actually call them ice structuring proteins.
By whatever name you call them, the proteins are yet another example of something very useful that came out of purely academic research.

Tuesday, January 7, 2014

Neurocrine Biosciences: Developing a Drug With a Huge Market

This morning, Neurocrine Biosciences shot up 79% on news that a study of their small molecule NBI-98854 to treat tardive dyskinesia (a disorder characterized by involuntary facial movements) is progressing well.  The drug targets and inhibits VMAT2, a solute carrier channel that transports monoamines at nerve synaptic junctions, including dopamine, norepinephrine, serotonin, and histamine.

Though tardive dyskinesia (TD) at first sounds similar to the symptoms of Parkinson's Disease, apparently they're very different, according to the Tardive Dyskinesia Center, which explains why the company isn't angling NBI-98854 as a possible drug for use in Parkinson's.  

Nevertheless, I don't think Parkinson's would have been the major market for Neurocrine's drug.  What makes NBI-98854 interesting is that the long term use of a variety of other drugs used to treat common conditions can lead to TD; take metclopramide (Reglan) for treatment of nausea and vomiting, or espesically Haloperidol (Haldol) as an example of many anti-psychotic drugs.  Here's a laundry list of about twenty drugs that can lead to TD (From The Dystonia Foundation).  

So while it still may be early to say Neurocrine is in the clear, it seems that with NBI-98854 the company is positioning itself to own a companion drug that'll be used in a wide variety of markets.  A very nice strategy indeed.