Deisseroth on new step ChR2

Nature methods has a small piece interviewing Karl Deisseroth on properties of the new step ChR2.

Some shortcomings of step ChR2 and future research directions:

Deisseroth expects ongoing efforts to improve key features of these channels. “One disadvantage is that some of the mutants have reduced current compared to wild type, so multiple mutations may help to bring those current levels back up to wild-type levels,” he says. Projects designed to improve membrane targeting and to apply a composite of opsins, including the red light–responsive channelrhodopsin from Volvox carteri, are also in the works in his laboratory.

A return to integrative medicine

Today’s NYT has a fascinating article about NIH‘s new Undiagnosed Diseases Program.

The program’s methodology is still evolving, but for the first dozen or so patients it worked this way: A primary-care physician sent in a letter describing the case, followed by reams of records documenting the diagnostic dead ends the patient had already confronted. Gahl personally reviewed all the cases and discarded about three-quarters of them, usually because the problem was insufficiently documented, seemed to be psychosomatic or, for some other reason, left Gahl with the impression that the N.I.H. had little new to offer. Then he took the most promising cases to his medical-review board, made up of several dozen clinical investigators from all over the N.I.H. The board reviewed 10 or so cases at each monthly meeting, out of which it accepted just a handful, the ones that seemed most likely to lead to a new insight into a known disease, or, even better, to a diagnosis of a disease never before seen. Then Gahl’s staff arranged to bring in each patient for a week of assessment in Bethesda. There, the patient would meet an array of specialists who did physical exams, took histories and conducted whatever additional tests they needed: ultrasound scans, M.R.I. scans, X-rays, electroencephalograms, maybe a spinal tap or a biopsy of skin or other tissue.

This approach seems in many ways more fruitful than bouncing patients from one specialist to another. Instead get the specialists together for a short period and focus on the patient. But even more tantalizing are the long-term goals:

Gahl’s projected success rate is so low because his aim is so high. His holy grail is a molecular diagnosis: finding not just a description of a new disease but also an understanding of how it works at the level of the gene. With this goal, the Undiagnosed Diseases Program aspires to be a model for how genomic medicine will be done in the 21st century.

The article documents NIH use of a “one-million SNP chip” on these patients and discovering potential molecular targets by combining insertion-deletion analysis with standard practice differential diagnosis. Combined with the recent addition of the National Center for Complementary and Alternative Medicine, NIH seems to be focusing on building clinical expertise in more integrative medicine.

Evidence of similar linguistic capabilities in Neaderthals

Apparently, in a few years, we will be able to bring Neaderthals back to life with the complete Neaderthal genome [NYT]. Currently, there is good sequence data available over 63% of the genome. (I’m amazed that, given fragmented DNA from bone, Neanderthal sequence can be distinguished from human DNA contamination but perhaps this problem is solved by having high enough coverage/multiple fragments of the same region.)

Also, it looks like Neanderthals share the FOXP2 variant that humans have:

Archaeologists have long debated whether Neanderthals could speak, and they have eagerly awaited Dr. Pääbo’s analysis of the Neanderthal FOXP2, a gene essential for language. Modern humans have two changes in FOXP2 that are not found in chimpanzees, and that presumably evolved to make speech possible. Dr. Pääbo said Neanderthals had the same two changes in their version of the FOXP2 gene. But many other genes are involved in language, so it is too early to say whether Neanderthals could speak.

UPDATE: A few days ago, I heard Wolf Enard, one of Paabo’s postdocs, speak on a fascinating project, where human version of FOXP2 was knocked in to mice (replacing the endogenous mouse version). Although the phenotypic effects were subtle, the approach itself is quite revolutionary: Putting human versions of genes into model organisms to see how the subsequent evolution of the gene changes its function. I wonder what other genes might be amenable to this approach.

Letting scientists off the leash

From Olivia Judson‘s NYT blog: Stanford’s Steve Quake proposes a new type of funding model that lets scientists focus on science.

The problem:

Such a system does not come without its own perils. It is not so easy to ask our young scientists to think out of the box when a significant portion of their salary (and mortgage payments) depends on guaranteeing a steady source of funding. Consequently, professors become highly attuned to the institutional priorities of various funding agencies — often at a cost to their own creativity and desired research directions.

Science at its most interesting is provocative, surprising, counter-intuitive and difficult to plan — and those are very difficult values to institutionalize in an organization or bureaucracy of any size. I have seen my own grant proposals get chewed up and rejected with comments like “typically bold, but wildly ambitious,” and wondered why it is wrong to be ambitious in one’s research — but perhaps that is a conclusion fully consistent with science by committee.

Conference on Neuroprosthetic Devices

The First International Conference on Neuroprosthetic Devices will take place at National Chiao Tung University, Hsinchu, Taiwan on March 19th and 20th, 2009. The mission of this newly founded conference is to foster West-East interaction and collaboration in the rapidly advancing clinical use of neuroprosthetics. The specific aim of the first conference is to expose unique technological and neurological research opportunities in Taiwan. National Chaio Tung University is one of the best universities in Taiwan and is located right next to the world-famous HsinChu Science Park hosting hundreds of biotechnology, semiconductor, and electronics companies.

The conference sessions will cover several key areas in the neuroprosthetic development, such as deep brain stimulation for treatment of Parkinson’s disease and epilepsy, devices for restoring hearing and overcoming muscle paralysis, microelectrode biocompatibility, and novel microelectrode technologies. For detailed conference program and registration information, please visit