“You Know, We’ve Always Had Been Nerds. I Was A Nerd In High School. I Was Like… I Didn’t Get

“You know, we’ve always had been nerds. I was a nerd in high school. I was like… I didn’t get beat up, I was invisible.”

New ways to mass produce human neurons for studying neuropsychiatric disorders

Scientists from Singapore have streamlined the process of using human stem cells to mass produce GABAergic neurons (GNs) in the laboratory. This new protocol provides scientists with a robust source of GNs to study many psychiatric and neurological disorders such as autism, schizophrenia, and epilepsy, which are thought to develop at least in part due to GN dysfunction.

GNs are inhibitory neurons that reduce neuronal activation, and make up roughly 20 per cent of the human brain. They work alongside excitatory neurons (ENs) to ensure balanced neural activity for normal brain function. The coordinated interplay between GNs and ENs orchestrate specific activation patterns in the brain, which are responsible for our behaviour, emotions, and higher reasoning. Functional impairment of GNs results in imbalanced neural activity, thereby contributing to the symptoms observed in many psychiatric disorders.

The availability of high quality, functional human GN populations would facilitate the development of good models for studying psychiatric disorders, as well as for screening drug effects on specific populations of neurons. Scientists worldwide have been hard at work trying to generate a consistent supply of GNs in the laboratory, but have been faced with many challenges. Protocols involving multiple complex stages, poor yield, and requiring a long time to generate mature and functional GNs are just some of the limitations encountered.

Many of these limitations have now been overcome by the development of a rapid and robust protocol to generate GNs from human pluripotent stem cells (hPSCs) in a single step. With the addition of a specific combination of factors, hPSCs turn into mature and functional GNs in a mere six – eight weeks. This is about two – three times faster than the 10 - 30 weeks required for previous protocols. In addition, this new protocol is highly efficient, with GNs making up more than 80 per cent of the final neuron population.

To develop this protocol, the team from Duke-NUS Medical School (Duke-NUS), A*STAR’s Genome Institute of Singapore (GIS) and the National Neuroscience Institute (NNI) first identified genetic factors involved in GN development in the brain. The team then tried many different combinations of these factors, and succeeded in confirming that mature and functional human GNs were indeed generated.

“Just like how a balance of Yin and Yang is needed in order to stay healthy, a balance of ENs and GNs is required for normal brain function. We now know a fair bit about ENs because we have good protocols to make them. However, we still know very little of the other player, the GNs, because current protocols do not work well. Yet, when these GNs malfunction our brain goes haywire,” commented Dr Alfred Sun, a Research Fellow at NNI and co-first author of the publication alongside Mr Qiang Yuan, an NUS Graduate School PhD student.

“Our quick, efficient and easy way to mass produce GNs for lab use is a game changer for neuroscience and drug discovery. With increased recognition of the essential role of GNs in almost all neurological and psychiatric diseases, we envisage our new method to be widely used to advance research and drug screening,” said Dr Shawn Je, Assistant Professor in the Neuroscience and Behavioural Disorders Programme at Duke-NUS, and senior author of the study.

The speed and efficiency of generating GNs with this new protocol provides researchers unprecedented access to the quantities of neurons necessary for studying the role of GNs in disease mechanisms. Drugs and small molecules may now be screened at an unparalleled rate to discover the next blockbuster treatment for autism, schizophrenia, and epilepsy.

Sketching out magnetism with electricity

In a proof-of-concept study published in Nature Physics, researchers drew magnetic squares in a nonmagnetic material with an electrified pen and then “read” this magnetic doodle with X-rays.

The experiment demonstrated that magnetic properties can be created and annihilated in a nonmagnetic material with precise application of an electric field – something long sought by scientists looking for a better way to store and retrieve information on hard drives and other magnetic memory devices. The research took place at the Department of Energy’s SLAC National Accelerator Laboratory and the Korea Advanced Institute of Science and Technology.

“The important thing is that it’s reversible. Changing the voltage of the applied electric field demagnetizes the material again,” said Hendrik Ohldag, a co-author on the paper and scientist at the lab’s Stanford Synchrotron Radiation Lightsource (SSRL), a DOE Office of Science User Facility.

“That means this technique could be used to design new types of memory storage devices with additional layers of information that can be turned on and off with an electric field, rather than the magnetic fields used today,” Ohldag said. “This would allow more targeted control, and would be less likely to cause unwanted effects in surrounding magnetic areas.”

How do you build a metal nanoparticle?

Novel theory explains how metal nanoparticles form

Although scientists have for decades been able to synthesize nanoparticles in the lab, the process is mostly trial and error, and how the formation actually takes place is obscure. However, a study recently published in Nature Communications by chemical engineers at the University of Pittsburgh’s Swanson School of Engineering explains how metal nanoparticles form.

“Thermodynamic Stability of Ligand-Protected Metal Nanoclusters” (DOI: 10.1038/ncomms15988) was co-authored by Giannis Mpourmpakis, assistant professor of chemical and petroleum engineering, and PhD candidate Michael G. Taylor. The research, completed in Mpourmpakis’ Computer-Aided Nano and Energy Lab (C.A.N.E.LA.), is funded through a National Science Foundation CAREER award and bridges previous research focused on designing nanoparticles for catalytic applications.

“Even though there is extensive research into metal nanoparticle synthesis, there really isn’t a rational explanation why a nanoparticle is formed,” Dr. Mpourmpakis said. “We wanted to investigate not just the catalytic applications of nanoparticles, but to make a step further and understand nanoparticle stability and formation. This new thermodynamic stability theory explains why ligand-protected metal nanoclusters are stabilized at specific sizes.”

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