Bring me those cells, and I want them alive! These neurons derived from skin cells could provide key insights into the development of Alzheimer's.

Researchers at UC San Diego have created a new weapon in the fight against Alzheimer’s: living neurons in the lab. Lead by Laurence Goldstein, director of UCSD’s Stem Cell Program, the team of scientists took fibroblasts from skin tissue to create induced pluripotent stem cells (iPSCs), which can become any mature cell in the body, including nerve cells. By harvesting fibroblasts from patients with Alzheimer’s, Goldstein and his colleagues were able to produce neurons that displayed clear tendencies towards developing the disease. Typical research requires harvesting brain tissue from dead patients, but these living cells provide a unique opportunity to study Alzheimer’s while it is still being developed. If this technique becomes widely adopted it will give researchers all over the world the samples they need to better understand, and possibly defeat, Alzheimer’s.

To effectively fight an enemy, one needs to know how they live. Researchers have been trying to conquer Alzheimer’s for decades, and in that pursuit have found many different ways to study the disease. Yet examining actual cells that have Alzheimer’s is difficult. Doctors simply won’t cut into a patient’s brain and remove tissue they think is affected. At least, not while that patient is alive. Yet postmortem study examines cells long after the disease has taken its course. What researchers need is a reliable way to study how Alzheimer’s develops in living cells as it happens. That’s where Goldstein and his colleagues come in. Their technique can take cells from patients with Alzheimer’s and create neurons outside of their bodies to be studied in the lab. No more messy brain autopsies, just living cells waiting to be examined. In the video below, Goldstein discusses more of the reasoning behind this research, as well as his team’s success:

Recently published in Nature, the work done at UC San Diego involved a small sample group: just six human sources for the cells. Goldstein and colleagues collected fibroblasts from two patients with the rare Familial Alzheimer’s Disease that is linked to genetic predisposition, two patients with Sporadic Alzheimer’s (thought to be not as genetically dependent), and two healthy people with no histories of neural disease. These skin cells were transformed into iPSCs and then into neurons. Nearly all of these transformed cells showed the activity expected for living nerve cells, including forming synaptic contacts. Satisfied with the vitality of the cells, UCSD researchers examined them for chemical markers linked to Alzheimer’s. In patient’s with the familial form of the disease they found higher levels of amyloid-β, phospho-tau, and active glycogen synthase kinase-3β – all proteins associated with the illness. Cells from one of the patients with the Sporadic variation also displayed some of these chemical indicators. While still very preliminary, the research indicates that these stem cell derived neurons could be a viable platform for studying the mechanisms involved in the onset of Alzheimer’s.

This study builds off of techniques in stem cell research that have only become available in the last few years. Induced pluripotent stem cells were first created in 2006. The process typically involves taking mature cells and using retroviruses to genetically alter them to become stem cells. As Singularity Hub discussed, by 2009 scientists had begun to debate whether fat cells or skin cells (i.e. fibroblasts) were better for transforming into iPSCs. The iPSC process is a great example of how a new technology can arise quickly and have a disruptive (and positive) impact on a field of science.

Yet with their recent arrival has come concerns over side effects of using iPSCs. In research unrelated to this study, iPSCs have been linked to increased risks for cells developing into cancer. More relevant, perhaps, are other concerns that the techniques used to create iPSCs may (in general) affect the creation of proteins in the final cell. In other words, critics worry that all this cellular alchemy may alter those chemical markers that scientists like Goldstein hope to examine.

Whether or not those concerns prove valid, there’s still great hope for beating Alzheimer’s through studying artificially created neurons in the lab. Even if iPSCs prove problematic, there are other ways of creating human neurons from fibroblasts (some of which were used in earlier experiments that agree with the UCSD study). No matter what technique is used, however, at some point soon it is very likely that scientists will be able to take skin samples from a wide variety of Alzheimer’s patients and family members and create lab-ready nerve cell specimens for examination. It will be like peeking inside someone’s brain chemistry without actually needing their brain on hand. There’s no guarantee that studying these cells will yield successful treatments for Alzheimer’s, but it makes logical sense that if you want to stop the disease in patients before it becomes life-destroying you need to understand how the disease begins. There may be a key protein, or gene, that if blocked early, could keep the cell from developing Alzheimer’s. It’s too soon to tell, but not too soon to hope.

[image credit: UC San Diego]
[video credit: UC San Diego]
[source: Israel et al Nature (2012), UC San Diego News]

The underwater drone swarm will eventually help researchers at UC San Diego explore the ocean (left). Right now, there are only five or six of the prototypes (right).

While the AUEs aren’t exactly articulated machines, they have many of the features and benefits of swarm robotics. As with many swarm robots, their strength is in numbers, and communication between individual bots. A solitary drone could only tell researchers about the conditions in its immediate vicinity. A fleet of drones will be able to describe their relative movement and the variations in ocean activity. It’s a cool concept that has great scalability. Right now Jaffe is planning on hundreds of drones, but imagine what we could learn with thousands or millions. The ocean is the last great frontier on Earth and these unmanned devices may be our best way of exploring it.

Jaffe is already building several prototypes for the AUE, including five or six of the soccer-ball sized ‘motherships’ and about 20 of a smaller version (the mini-AUE). The smaller and larger drones will be able to communicate via acoustic signals. A single mothership AUE could be moored while talking to free floating AUEs and mini-AUEs. The larger drones may have GPS trackers, while the smaller would not. This sort of network would allow Jaffe to measure ocean drift.

Other researchers have built buoyant drones before, some even more sophisticated. Yet none have taken measurements over the distance or period of time that Jaffe’s will. By dispersing a swarm of AUEs and mini-AUEs, Jaffe’s team could get a unique spatial and temporal understanding of the ocean.

Here's a better look at what's going on inside the AUE.

The following video is a presentation Jaffe gave explaining his AUE project. It’s a bit long and may not appeal to those unaccustomed to listening to scientific lectures. You can skip to 26:30 to hear Jaffe introduce the AUE device. He describes the mini-AUE (and shows a prototype) around 31:15. If you stick around to 38:25 and 47:30 he’ll tell you about the use of AUEs to locate plane crashes, and how building a mini-AUE might become a great project for middle school and high school students.

As Jaffe briefly described in the video, the AUEs could be modified with different kinds of instrumentation. They may measure salinity, dissolved oxygen, pH, chlorophyll levels, or turbidity of water. Each of these variables has a significant effect on ocean life. Taken collectively they could give a detailed account of marine habitats, helping governments decide if protected areas of the ocean are thriving.

But there’s really no limit to what these drones could learn. Biological info on marine habitats, meteorological on currents, seismological measurements on underwater earthquakes…the list goes on. Which is probably why the NSF has given Jaffe and his colleagues another $1.5 million to help with the control mechanisms for the movement of the AUEs. Each little drone is just a ball bobbing along under the water’s surface. As a collective they could be a vast net to catch all the secrets of the ocean. Maybe they’ll finally be able to tell me where the monster from Cloverfield came from.

[photo credit: Jaffe Lab, UCSD]
[video credit: UCTV]

University of California San Diego is organizing a collectively-created visual model of the mouse brain. Open up, Mickey, it's time to see what's inside.

It may sound like the premise for the next roller coaster ride at Disney Land, but UC San Diego is serious about letting you take a virtual voyage through the brain of a mouse. Their new open source resource, called the Whole Brain Catalog, allows scientists to navigate through a visual model of a mouse brain. Not only that, but each research team can also upload their latest results helping to improve the accuracy of the WBC overtime. UCSD hopes that their new creation will prove to be a valuable utility for scientists all over the world. Watch a brief demo of the catalog in the video after the break.

Much like MIT’s Registry for Standard Biological Parts, or even Google Earth, the Whole Brain Catalog hopes to build off of collective knowledge. Individual research groups contributing to a central repository of information is going to change the way the scientific community works. In the short term, teams around the world will have access to a visual model of the brain that is used most often in their labs. In the long term, the success of WBC could help usher in a new era of the rapid exchange of scientific information. The quicker that researchers can share their results, the faster other teams can benefit from them, and the sooner we will all enjoy the technological innovations they create.

The video tour you just watched is a cool visual trek, but it doesn’t really highlight all of the capabilities that the Whole Brain Catalog will contain. Yes, the resource will be multi-scale, letting you explore the brain as a whole, or in components right down to the subcellular level. Just as importantly though, it will be open source, and downloadable – giving researchers easy access and a chance to edit its contents. Those contents will be searchable, so that you can type in “hypothalamus” and jump straight to that portion of the mouse brain.

Rather amazingly, the WBC will be at such high resolution that it will be able to simulate neural connections. By building off the scientific results of various teams around the world, these simulations could help form a highly accurate model of a functioning mammalian brain. No small feat.

The WBC shares some ultimate goals of human brain simulators like the Blue Brain Project. Mouse brains, however, offer some unique advantages. They are simpler, more easily explored, and researchers in many countries have a shared standard by which they are examined and discussed. Eventually, the information included in the Whole Brain Catalog could make it a unique resource for neurological studies, made all the more special and powerful by its open source nature. It’s much too early to tell if UC San Diego’s attempt will ultimately be successful, but I wish it luck. And if Disney wants to start on making an associated ride, I have some ideas already: 3D Neuron Laser Tag. It’ll be amazing, trust me.

[screen capture and video credit: Whole Brain Catalog]