Russian supercomputer model describes the dynamic instability of microtubules

Researchers of Sechenov University together with their colleagues from several Russian institutes studied the dynamics of microtubules that form the basis of the cytoskeleton and take part in the transfer of particles within a cell and its division. The supercomputer model they developed describes the mechanical properties of protofilaments (longitudinal fibers that compose microtubules) and suggests how they assemble and disassemble. All the details of the study can be found in PLOS Computational Biology.

Microtubules are long hollow cylinders with walls consisting of tubulin molecules arranged helix-wise. Each cycle contains 13 pairs of α- and β-tubulin, so a microtubule is composed of 13 longitudinal fibers, protofilaments. Microtubules grow by the addition of tubulin from the cytoplasm. The protein binds more actively to one end (plus-end) of the microtubule and dissociates from the other one (minus-end) quicker. Both processes take place simultaneously, but their rate changes: when the concentration of tubulin is sufficient, microtubules grow faster than degrade, and when the concentration is low - vice versa. Between the phases of growth and shrinking, there is a period of stability, but it is very short. 

Though the mechanisms of microtubule's growth and shortening are well-studied, there are still quite a few questions about how the structure and properties of tubulin change. It is known that both molecules of tubulin (α- and β-tubulin) are connected to a molecule of guanosine triphosphate (GTP). GTP of β-tubulin can hydrolyze and turn into guanosine diphosphate (GDP) that causes the double tubulin molecule (dimer) to dissociate from a microtubule. The authors of the paper tried to understand how the properties of tubulin dimers and protofilaments depend on GTP hydrolysis and what provides the difference between plus- and minus-ends of microtubules. Above all, microtubules take part in cell division, and studies of these mechanisms will contribute to the search for yet unknown ways to suppress the replication of cancer cells. In particular, microtubules serve as molecular targets for an important anti-tumor drug, paclitaxel, that inhibits microtubule disassembly. {module INSIDE STORY}

Existing studies offer several models of possible changes in protein structure taking place upon GTP hydrolysis: a slight curving of tubulin dimers or weakening of longitudinal bonds between dimers without significant changes in their shape. Some researchers also suggest that hydrolysis may affect interactions between neighboring protofilaments. According to the authors, it was impossible to prove or refute any of these claims for a long time because of the lack of precise experimental data. In this research, they verified the first hypothesis and computed the 'behavior' of molecules using the latest available experimental structures obtained by cryo-electron tomography. They examined bonds between dimers as well as between α- and β-tubulin within them.

Scientists modeled the bending of the tubulin dimer and the whole protofilament, with GTP and GDP bound to them, throughout one millisecond, watching the angle and direction of the curvature and assessing the strength of bonds within and between dimers. The results showed that protofilaments with GTP and GDP-bound tubulin were bent almost to the same extent, so the first hypothesis was disproved. But it turned out that GTP influences the flexibility of the bonds between dimers: protofilaments made of tubulin connected with GTP were much more bendable compared with those containing GDP.

Using the revealed difference in bond rigidity between GTP and GDP-connected protofilaments, the authors concluded that more flexible bonds ease the straightening of protofilaments and thus facilitate the assembly of the microtubule.

'Based on simulations, we developed a simple model of dynamic instability of microtubules, i.e. their assembly and disassembly. A deeper understanding of this process on the molecular level would enable a targeted development of medicines able to affect the stability of microtubules and thus prevent the reproduction of tumour cells', said Philipp Orekhov, co-author of the paper and senior scientist at the Institute for Personalized Medicine, Sechenov University.

Curtin astrophysicist uses the Pawsey Supercomputing Centre, outback telescope to capture Milky Way center, discovers remnants of dead stars

A radio telescope in the Western Australian outback has captured a spectacular new view of the center of the galaxy in which we live, the Milky Way.

The image from the Murchison Widefield Array (MWA) telescope shows what our galaxy would look like if human eyes could see radio waves.

Astrophysicist Dr. Natasha Hurley-Walker, from the Curtin University node of the International Centre for Radio Astronomy Research (ICRAR), created the images using the Pawsey Supercomputing Centre in Perth.

"This new view captures low-frequency radio emission from our galaxy, looking both in fine detail and at larger structures," she said.

"Our images are looking directly at the middle of the Milky Way, towards a region astronomers call the Galactic Centre."

The data for the research comes from the Galactic and Extragalactic All-sky MWA survey, or 'GLEAM' for short. This image shows a new view of the Milky Way from the Murchison Widefield Array, with the lowest frequencies in red, middle frequencies in green, and the highest frequencies in blue. Huge golden filaments indicate enormous magnetic fields, supernova remnants are visible as little spherical bubbles, and regions of massive star formation show up in blue. [The supermassive black hole at the centre of our galaxy is hidden in the bright white region in the centre.]{module INSIDE STORY}

The survey has a resolution of two arcminutes (about the same as the human eye) and maps the sky using radio waves at frequencies between 72 and 231 MHz (FM radio is near 100 MHz).

"It's the power of this wide frequency range that makes it possible for us to disentangle different overlapping objects as we look toward the complexity of the Galactic Centre," Dr. Hurley-Walker said.

"Essentially, different objects have different 'radio colors', so we can use them to work out what kind of physics is at play."

Using the images, Dr. Hurley-Walker and her colleagues discovered the remnants of 27 massive stars that exploded in supernovae at the end of their lives.

These stars would have been eight or more times more massive than our Sun before their dramatic destruction thousands of years ago.

Younger and closer supernova remnants, or those in very dense environments, are easy to spot, and 295 are already known.

Unlike other instruments, the MWA can find those which are older, further away, or in very empty environments.

Dr. Hurley-Walker said one of the newly-discovered supernova remnants lies in such an empty region of space, far out of the plane of our galaxy, and so despite being quite young, is also very faint.

"It's the remains of a star that died less than 9,000 years ago, meaning the explosion could have been visible to Indigenous people across Australia at that time," she said.

An expert in cultural astronomy, Associate Professor Duane Hamacher from the University of Melbourne, said some Aboriginal traditions do describe bright new stars appearing in the sky, but we don't know of any definitive traditions that describe this particular event.

"However, now that we know when and where this supernova appeared in the sky, we can collaborate with Indigenous elders to see if any of their traditions describe this cosmic event. If any exist, it would be extremely exciting," he said.

Dr. Hurley-Walker said two of the supernova remnants discovered are quite unusual "orphans", found in a region of the sky where there are no massive stars, which means future searches across other such regions might be more successful than astronomers expected.

Other supernova remnants discovered in the research are very old, she said.

"This is really exciting for us because it's hard to find supernova remnants in this phase of life--they allow us to look further back in time in the Milky Way."

The MWA telescope is a precursor to the world's largest radio telescope, the Square Kilometre Array, which is due to be built in Australia and South Africa from 2021.

"The MWA is perfect for finding these objects, but it is limited in its sensitivity and resolution," Dr Hurley-Walker said.

"The low-frequency part of the SKA, which will be built at the same site as the MWA, will be thousands of times more sensitive and have much better resolution, so should find the thousands of supernova remnants that formed in the last 100,000 years, even on the other side of the Milky Way."

Cyxtera elevates Medina to executive chairman, promotes Fonseca to CEO

Cyxtera Technologies has announced that Cyxtera founder and CEO Manuel D. Medina has been elevated to the position of Executive Chairman for both Cyxtera and its recently announced AppGate spin-out, where he will provide strategic guidance and counsel for the two companies. Current Cyxtera President & Chief Operating Officer Nelson Fonseca has been promoted to the role of CEO for Cyxtera.

Fonseca has more than 20 years of experience as an executive in the I.T. infrastructure sector. He served in several leadership positions alongside Medina at Terremark, ultimately as President of the Verizon Terremark unit after Verizon’s acquisition of the company for an enterprise value of $2 billion.

“I’m excited to have the opportunity to lead a great company and global provider of colocation services,” said Fonseca. “The team and I look forward to building on our position as a market leader in retail colocation by expanding our highly-connected data center footprint, broadening our global partner ecosystem and further innovating our CXD platform to deliver a truly world-class customer experience.” {module INSIDE STORY}

“Our recently announced spin out of our cybersecurity business positions both Cyxtera and AppGate to take advantage of unique and substantial growth opportunities and to drive innovation and change into their respective sectors,” said Medina. “I’m looking forward to working closely with both teams as we continue to transform the cybersecurity and data center industries, and I am delighted that my long-time friend and colleague Nelson Fonseca will take the reins as Cyxtera CEO.”