Tyler O'Neal, Staff Editor BIG DATA

BU medicine builds a better lung model

May lead to new personalized treatments for lung diseases

In Boston, using a combination of pluripotent stem cells (cells that can potentially produce any cell or tissue type) and machine learning (artificial intelligence that allows supercomputers to learn automatically), researchers have improved how they generate lung cells.

Using this technique, cells can be grown in a laboratory and stored for more than one year without losing their lung identity and used to model lung diseases thereby finding better treatments and cures for lung diseases in the future.

Induced pluripotent stem (iPS) cells are derived from the donated skin or blood cells of adults and, with the reactivation of four genes, are reprogrammed back to an embryonic stem cell-like state. iPS cells can be differentiated toward any cell type in the body and do not require the use of embryos.

{module INSIDE STORY} Building on previous work from the Center for Regenerative Medicine (CReM) of Boston University and Boston Medical Center, researchers in the CReM, working together with investigators from Carnegie Mellon University (CMU), reprogrammed blood from adults into iPS cells. They then treated these stem cells with growth factors over a period of one month until they became cells that were very similar to adult lung cells.

According to the researchers, often when this type of experiment is performed the resulting cells are not a pure collection of the cell that they aimed to create (target cell) and they do not keep the characteristics of the target cell for prolonged periods of time.

"Therefore, we developed a combination of techniques that examines the gene expression of thousands of single cells combined with DNA barcoding of each individual cell and machine learning to build up a dynamic picture of what factors favor cells that go on to be lung cells in our system. Using this knowledge we were able to improve our methods for generating lung cells so that we can now create more relevant cells that keep their cell identity in a dish for more than one year," explained Killian Hurley, MD, PhD, researcher at the Royal College of Surgeons in Ireland, who co-authored the study with Jun Ding, PhD, a post-doctoral fellow at CMU.

The researchers believe this study will improve their ability to model lung disease and treatments in the laboratory for diseases including idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), alpha-1 antitrypsin deficiency and neonatal respiratory distress or early-onset interstitial lung disease.

Millions of people in the United States and around the world have severe lung diseases, often without good treatments or cure. Some of these diseases may even require lung transplantation which is a complex and high-risk surgery with the need for donor organs always exceeding the supply.

"The machine learning methods we developed for this study can also be applied to studies of other tissues and organs," said Ding. "We hope that our newly developed techniques for generating a pure, unlimited supply of cells using patients-derived stem cells can make possible new treatments or cures for diseases. These developments would prolong lives and improve the quality of those lives."

"The key hurdle to understanding what goes wrong with an individual patient's lung cells has been our inability to access those cells or to grow them in the laboratory. This approach allows us to now engineer from any individual patient those very finicky cells and to introduce bar codes into those cells that allow us to track and understand each cell and all their progeny over time in the laboratory dish. The result is an inexhaustible source of new lung cells that can be prepared from any patient of any age," added co-corresponding author Darrell Kotton, MD, David C. Seldin Professor of Medicine and Director, CReM, who led the work together with Ziv Bar-Joseph, PhD, the FORE Systems Professor of Computer Science at CMU.

Russian biophysicists find 'extra' component in molecular motor

Tyler O'Neal, Staff Editor BIG DATA

Researchers from the Moscow Institute of Physics and Technology have discovered an additional component in ATP synthase, a molecular machine that produces the energy-conserving compound in all cellular organisms. 

In order to store energy, living cells rely on a molecule called ATP. It is produced by ATP synthase, a molecular-scale motor comprised of a rotor and a stator. Such machines are nested in the inner membranes of mitochondria and chloroplasts in most organisms, including animals, plants, and bacteria. The rotor component resembles a barrel embedded into a biological membrane. This "barrel," or C-ring, is made of between eight and 17 so-called protomers. Their exact number depends on the organism.

MIPT researchers and their colleagues from Grenoble, France, have obtained a first-ever high-resolution structure of the C ring from spinach chloroplasts. As the supercomputer model of the C ring was taking shape, the biophysicists spotted something peculiar. The new unique features of the ATP synthase structure are described in detail in a paper in an educational journal. Overall view of the additional elements inside the C ring: side view (A), C ring cross section (B), from above (C), additional element details (D). The protein subunits C are shown as colored spirals.{module INSIDE STORY}

"We noticed additional circle-shaped elements inside the C ring," said MIPT doctoral student Alexey Vlasov from the Institute's Research Center for Molecular Mechanisms of Aging and Age-Related Diseases. "At first we thought that was an artifact. But when we looked through the C ring structures obtained by other scientists for various organisms, the circles turned up again, time after time."

It came as a surprise for the researchers that previous studies did not pay attention to the circles inside C rings. Up until now, their nature remained unexplained.

"This study speaks to the fact that no minor detail is negligible in science. Even a subtle feature, spotted in due course, might lead to a breakthrough discovery," noted Valentin Gordeliy, who heads research groups at the Institute of Structural Biology in Grenoble (France) and Jülich Research Center (Germany) and is the scientific coordinator of the MIPT Research Center for Molecular Mechanisms of Aging and Age-Related Diseases.

The biophysicists from MIPT set out to solve the C ring puzzle. Supercomputer modeling and biochemical experiments indicated that the ring contained quinone molecules. They act as electron carriers in biological systems. Some of the examples are plastoquinone, found in chloroplasts, and the coenzyme Q in mitochondria.

Biologists have long known that the C ring of ATP synthase does not have a "hole" in it. So while some molecules were expected to exist on the inside, no one was sure which exactly. The finding proved unexpected: quinones.

While the discovery is interesting in and of itself, researchers have yet to determine why the C ring hosts quinones and how they get there. One theory suggests C rings can function as pores in mitochondrial membranes. Such a pore might open when the cell death process is initiated. Can the quinones in a C ring kill a cell? This is a question for the MIPT biologists to address in their further research.

BGN Technologies demos first all-optical, stealth encryption technology at the Cybertech Global Tel Aviv conference

Tyler O'Neal, Staff Editor BIG DATA

BGN Technologies, the technology-transfer company of Ben-Gurion University of the Negev (BGU), Israel, has introduced the first all-optical "stealth" encryption technology that will be significantly more secure and private for highly sensitive cloud-supercomputing network transmission. The new all-optical encryption innovation will be introduced at the Cybertech Global Tel Aviv conference taking place on January 28-30, 2020 in Tel Aviv, Israel.

"Today, information is still encrypted using digital techniques, although most data is transmitted over distance using light spectrum on fiber-optic networks," says Prof. Dan Sadot, Director of the Optical Communications Research Laboratory, who heads the team that developed the groundbreaking technology.

"Time is running out on security and privacy of digital encryption technology, which can be read offline if recorded and code-broken using intensive computing power. We've developed an end-to-end solution providing encryption, transmission, decryption, and detection optically instead of digitally." {module INSIDE STORY}

Using standard optical equipment, the research team essentially renders the fiber-optic light transmission invisible or stealthy. Instead of using one color of the light spectrum to send one large data stream, this method spreads the transmission across many colors in the optical spectrum bandwidth (1,000 x wider than digital) and intentionally creates multiple weaker data streams that are hidden under noise and elude detection.

Every transmission -- electronic, digital or fiber -- has a certain amount of "noise." The researchers demonstrated that they can transmit weaker encrypted data under a stronger inherent noise level that cannot be detected.

The solution also employs a commercially available phase mask, which changes the phase of each wavelength (color). That process also appears as noise, which destroys the "coherence" or ability to recompile the data without the correct encryption key. The optical phase mask cannot be recorded offline, so the data is destroyed if a hacker tries to decode it.

"Basically, the innovative breakthrough is that if you can't detect it, you can't steal it," Prof. Sadot says. "Because an eavesdropper can neither read the data nor even detect the existence of the transmitted signal, our optical stealth transmission provides the highest level of privacy and security for sensitive data applications."

Zafrir Levy, senior vice president for exact sciences and engineering at BGN, says, "The novel, patented method invented by Prof. Sadot and his team is highly useful for multiple applications, such as high-speed communication, sensitive transmission of financial, medical or social media-related information without the risk of eavesdropping or jamming data flow. In fact, with this method, an eavesdropper will require years to break the encryption key. BGN is now seeking an industry partner to implement and commercialize this game-changing technology."

"Every data center has 100G and 400G lines, and part of those lines are encrypted end-to-end," Prof. Sadot adds. "There is a need for non-digital encryption for customers who require the most advanced security possible."

This all-optical technology is an extension of the digital optical encryption method originally invented by Prof. Sadot and his team in collaboration with Prof. Zalevsky at Bar Ilan University.