cells – Page 2 – Lightsources.org

Microfluidic mixing chips can reveal how biomolecules interact

2018/07/312018/09/05

Christopher Flynn, a fourth year student majoring in Physics and Mathematics at Fort Lewis College, and a SUnRiSE student at Cornell this summer, is contributing to the design of microfluidic mixing chips which could significantly enhance our understanding of proteins and living cells.

Microfluidic mixing chips are used by scientists to analyze biological molecules. They have small channels in which biological solutions, usually solutions of protein, are mixed. Biological small angle x-ray solution scattering (BioSAXS) is then used to study how these biomolecules change under different conditions, for example when they mix with hormones and drugs or when they interact with other biomolecules. These observations can help further our understanding of how cells function.

With the intention of opening a door to the inner workings of cells, Flynn and Gillilan are continuing the work of Gillilan’s former postdoctoral student, Jesse Hopkins, who started a project on microfluidic chips more than two years ago. Hopkins was working on fabricating chips that could be used to observe molecular interactions and structural changes on a millisecond scale.

While Hopkins successfully designed almost every aspect of the chip, he was unable to get the final x-ray transparent window fixed on the chip without it leaking. Flynn’s main task over the summer is to resolve this. He creates chips in the Cornell NanoScale Science and Technology Facility (CNF), using techniques including photolithography and lamination. The chips have different layers, the faulty transparent window being in one of the last. After the first few layers of the chips are made, Flynn uses them to investigate different possibilities for the window. He expects to test these windows by pumping liquids through the chips, and if they have been fit successfully, to compare any results to computer simulations that Hopkins had developed.

Image: Richard Gillilan and Topher Flynn. The channels of the mixing chips are 30 microns wide, 500 microns deep.; a difficult feat but important feature of the chip.

Open and shut: pain signals in nerve cells

2018/07/232018/07/24

Our daily function depends on signals traveling between nerve cells (neurons) along fine-tuned pathways. Central nervous system neurons contain acid-sensing ion channel 1a (ASIC1a), a protein important in sensing pain and forming memories of fear. An ion channel lodged in the cell membrane that provides a pathway for sodium ions to enter the cell, ASIC1a opens and closes in response to changes in extracellular proton concentrations. When protons accumulate outside the neuron, the channel opens, allowing sodium ions to flow into the cell, depolarizing the cell membrane and generating an electrical signal. The channel eventually becomes desensitized to protons and the gate closes. Scientists have visualized both the open and desensitized channel structures, but the third structure, which forms when the protons dissipate and the channel closes, remained elusive. Using protein crystallography at the ALS, researchers finally visualized the closed channel.

Animation: As the proton concentration increases or decreases, the gated channel ASIC1a toggles between open and closed positions, controlling the timing of signals traveling through the cell membrane of one neuron en route to the next.

An electrifying view on catalysis

2018/07/032018/07/12

The future of chemistry is ‘electrifying’: With increasing availability of cheap electrical energy from renewables, it will soon become possible to drive many chemical processes by electrical power. In this way, chemical products and fuels can be produced via sustainable routes, replacing current processes which are based on fossil fuels.

In most cases, such electrically driven reactions make use of so-called electrocatalysts, complex materials which are assembled from a large number of chemical componentAs. The electrocatalyst plays an essential role: It helps to run the chemical reaction while keeping the loss of energy minimal, thereby saving as much renewable energy as possible. In most cases, electrocatalysts are developed empirically and the chemical reactions at their interfaces are poorly understood. A better understanding of these processes is essential, however, for fast development of new electrocatalysts and for a directed improvement of their lifetime, one of the most important factors that currently limit their applicability.

>Read more on the Elettra website

Figure: Introducing well-defined model electrocatalysts into the field of electrochemistry.

Google Maps for the cerebellum

2018/06/282018/07/12

A team of researchers from Göttingen has successfully applied a special variant of X-ray imaging to brain tissue. With the combination of high-resolution measurements at DESY’s X-ray light source PETRA III and data from a laboratory X-ray source, Tim Salditt’s group from the Institute of X-ray Physics at the Georg August University of Göttingen was able to visualize about 1.8 million nerve cells in the cerebellar cortex. The researchers describe the investigations with the so-called phase contrast tomography in the Proceedings of the National Academy of Sciences (PNAS).
The human cerebellum contains about 80 percent of all nerve cells in 10 percent of the brain volume – one cubic millimeter can therefore contain more than one million nerve cells. These process signals that mainly control learned and unconscious movement sequences. However, their exact positions and neighbourhood relationships are largely unknown. “Tomography in the so-called phase contrast mode and subsequent automated image processing enables the cells to be located and displayed in their exact position,” explains Mareike Töpperwien from the Institute of X-ray Physics at the University of Göttingen, lead author of the publication.

Image: Result of the phase contrast X-ray tomography at DESY’s X-ray source PETRA III.
Credit: Töpperwien et al., Universität Göttingen

Probing tumour interiors

2018/06/192018/06/21

X-ray fluorescence mapping to measure tumour penetration by a novel anticancer agent.

A new anticancer agent developed by the University of Warwick has been studied using microfocus synchrotron X-ray fluorescence (SXRF) at I18 at Diamond Light Source. As described in The Journal of Inorganic Biochemistry, researchers saw that the drug penetrated ovarian cancer cell spheroids and the distribution of zinc and calcium was perturbed.

Platinum-based chemotherapy agents are used to treat many cancer patients, but some can develop resistance to them. To address this issue, scientists from the University of Warwick sought to employ alternative precious metals. They developed an osmium-based agent, known as FY26, which exhibits high potency against a range of cancer cell lines. To unlock the potential of this novel agent and to test its efficacy and safety in clinical trials, the team need to fully understand its mechanism of action.

To explore how FY26 behaves in tumours, the team grew ovarian cancer spheroids and used SXRF at I18 to probe the depth of penetration of the drug. They noted that FY26 could enter the cores of the spheroids, which is critical for its activity and very encouraging for the future of the drug. SXRF also enabled them to probe other metals within the cells, which showed that the distribution of zinc and calcium was altered, providing new insights into the mechanism of FY26-induced cell death.

Figure: (extract) A) Structure of FY26and related complexes, [(ŋ⁶-p-cym)Os(Azpy-NMe₂)X]⁺. B) Bright field images and SXRF elemental maps of Os, Ca and Zn in A2780 human ovarian carcinoma spheroid sections (500 nm thick) treated with 0.7 µM FY26(½ IC₅₀) for 0 or 48 h. Raster scan: 2×2 µm² step size, 1 s dwell time. Scale bar 100 µm. Calibration bar in ng mm^-2. Yellow squares in bright field images indicate areas of the spheroid studied using SXRF. Red areas in SXRF elemental maps indicate the limits of the spheroids. C) Average Os content (in ng mm^-2) as a function of distance from A2780 3D spheroid surface, after treatment for 16 h (green), 24 h (blue) or 48 h (red) with 0.7 µM FY26.

Perovskites, the rising star for energy harvesting

2018/06/052018/06/18

Perovskites are promising candidates for photovoltaic cells, having reached an energy harvesting of more than 20% while it took silicon three decades to reach an equivalent. Scientists from all over the world are exploring these materials at the ESRF.

Photovoltaic (PV) panels exist in our society since several years now. The photovoltaic market is currently dominated by wafer-based photovoltaics or first generation PVs, namely the traditional crystalline silicon cells, which take a 90% of the market share.

Although silicon (Si) is an abundant material and the price of Si-PV has dropped in the past years, their manufacturing require costly facilities. In addition, their fabrication typically takes place in countries that rely on carbon-intensive forms of electricity generation (high carbon footprint).

But there is room for hope. There is a third generation of PV: those based on thin-film cells. These absorb light more efficiently and they currently take 10% of the market share.

Image: The CEA-CNRS team on ID01. From left to right: Peter Reiss, from CEA-Grenoble/INAC, Tobias Schulli from ID01, Tao Zhou from ID01, Asma Aicha Medjahed, Stephanie Pouget (both from CEA-Grenoble/INAC) and David Djurado, from the CNRS.
Credits: C. Argoud.

Fighting malaria with X-rays

2018/04/252018/04/25

Today 25 April, is World Malaria Day.

Considered as one of humanity’s oldest life-threatening diseases, nearly half the world population is at risk, with 216 million people affected in 91 countries worldwide in 2016. Malaria causes 445 000 deaths every year, mainly among children. The ESRF has been involved in research into Malaria since 2005, with different techniques being used in the quest to find ways to prevent or cure the disease.

Malaria in humans is caused by Plasmodium parasites, the greatest threat coming from two species: P. falciparum and P. vivax. The parasites are introduced through the bites of infected female Anopheles mosquitoes. They travel to the liver where they multiply, producing thousands of new parasites. These enter the blood stream and invade red blood cells, where they feed on hemoglobin (Hgb) in order to grow and multiply. After creating up to 20 new parasites, the red blood cells burst, releasing daughter parasites ready for new invasions. This life cycle leads to an exponential growth of infected red blood cells that may cause the death of the human host.

The research carried out over the years at the ESRF has aimed to identify mechanisms critical for the parasite’s survival in the hope of providing an intelligent basis for the development of drugs to stop the parasite’s multiplication and spread.

>Read more on the European Synchrotron website

Image: Inside the experimental hutch of the ESRF’s ID16A nano-analysis beamlin.
Credit: Pierre Jayet

Insights into the development of more effective anti-tumour drug

2018/04/182018/04/23

Natural killer cells are powerful weapons our body’s immune systems count on to fight infection and combat diseases like cancer, multiple sclerosis, and lupus. Finding ways to spark these potent cells into action could lead to more effective cancer treatments and vaccines.

While several chemical compounds have shown promise stimulating a type of natural killer cells, invariant natural killer T cells (iNKT) cells in animal models, their ability to activate human iNKT cells has been limited.

Now, an international team of top immunologists, structural biologists, and chemists published in Cell Chemical Biology the creation of a new compound that appears to have the properties researchers have been looking for. The research was co-led by Monash Biomedicine Discovery Institute’s (BDI) Dr Jérôme Le Nours, University of Connecticut’s Professor Amy Howell and Albert Einstein College of Medicine’s Dr Steve Porcelli. Dr Le Nours used the Micro Crystallography beamline (MX2) at the Australian Synchrotron as part of the study.

The compound – a modified version of an earlier synthesized ligand – is highly effective in activating human iNKT cells. It is also selective – encouraging iNKT cells to release a specific set of proteins known as Th1 cytokines, which stimulate anti-tumour immunity.

Image: 3D structure of proteins behind interaction of new drug that stimulates immune response to cancer cells. (Entire image here)

Success in clinical trials driving a shift in the treatment of blood cancers

2018/04/132018/04/23

The Australian Synchrotron is proud to be growing Australia’s capacity for innovative drug development, facilitating the advance of world-class disease and drug research through to local drug trials. Recent success in clinical trials of Venetoclax, the chronic lymphocytic leukaemia (CLL) drug developed by researchers from the Walter and Eliza Hall Institute and two international pharmaceutical companies is driving a major shift in the treatment of a range of blood cancers, according to a media information from the Peter MacCallum Cancer Centre.

Unravelling the great vision of flies

2018/04/092018/04/13

Fruit flies have a much better vision than what was previously believed in the scientific community.

Researchers from the University of Sheffield (UK), the University of Oulu (Finland), Max IV (Sweden) and University of Szeged (Hungary) are on ID16B trying to find out what happens in the photoreceptors in these insects’ eyes.

“It had always been claimed that fly’s eyesight was very basic, but I couldn’t believe that after so many centuries of evolution this was still the case”, explains Mikko Juusola, head of the Centre for Cognition in Small Brains at Sheffield University. So he started studying vision in fruit flies a decade ago and last year himself and his team debunked previous hypothesis: they proved that insects have a much better vision and can see in far greater detail than previously thought.

Insects’ compound eyes typically consist of thousands of tiny lens-capped ‘eye-units’, which together should capture a low-resolution pixelated image of the surrounding world. In contrast, the human eye has a single large lens, and the retinal photoreceptor array underneath it is densely-packed, which allows the eye to capture high-resolution images. This is why it was believed that insects did not have a good eyesight. Until Juusola came in the picture.

Image: Marko Huttula (University of Oulu, Finland), Jussi-Petteri Suuronen (ESRF) and Mikko Juusola (University of Sheffield, UK) on ESRF’s ID16B beamline. Credit: ©ESRF/C.Argoud

Scientists develop sugar-coated nanosheets to target pathogens

2018/03/292018/04/12

Molecular Foundry-designed 2-D sheets mimic the surface of cells

Researchers have developed a process for creating ultrathin, self-assembling sheets of synthetic materials that can function like designer flypaper in selectively binding with viruses, bacteria, and other pathogens.
In this way the new platform, developed by a team led by scientists at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), could potentially be used to inactivate or detect pathogens.

The team, which also included researchers from New York University, created the synthesized nanosheets at Berkeley Lab’s Molecular Foundry, a nanoscale science center, out of self-assembling, bio-inspired polymers known as peptoids. The study was published earlier this month in the journal ACS Nano.
The sheets were designed to present simple sugars in a patterned way along their surfaces, and these sugars, in turn, were demonstrated to selectively bind with several proteins, including one associated with the Shiga toxin, which causes dysentery. Because the outside of our cells are flat and covered with sugars, these 2-D nanosheets can effectively mimic cell surfaces.

Image: A molecular model of a peptoid nanosheet shows loop structures in sugars (orange) that bind to the Shiga toxin (shown as a five-color bound structure at upper right).
Credit: Berkeley Lab

Study reveals mechanism in spruce tree that causes growth

2018/02/162018/02/19

While it’s common knowledge that trees grow when days start to become longer in the springtime and stop growing when days become shorter in the fall, exactly how this happens has not been well understood.

Now, scientists using the Canadian Light Source are offering insights into the mechanisms of how certain cells in the winter buds of Norway spruce respond to changes in seasonal light, affecting growth. The research was published in Frontiers in Plant Science.

Such knowledge allows for better predictions of how trees might respond to climate change, which could bring freezing temperatures while daylight is still long or warmer temperatures when daylight is short.

Professor Jorunn E. Olsen and YeonKyeong Lee, plant scientists at the Norwegian University of Life Sciences, along with colleagues from the University of Saskatchewan investigated winter bud cells from Norway spruce and how they differ with respect to the amount of daylight to which they were exposed.

Image (from left to right, extract): plant with terminal winter bud after short day exposure for three weeks; plant with brown bud scales after short day exposure for eight weeks; plant showing bud break and new growth three weeks after re-transfer to long days following eight weeks under short days. Entire picture here.

Supporting World Cancer Day 2018

2018/02/032018/02/05

Diamond is proud to be supporting World Cancer Day and highlighting our role, working with our user community, in pioneering synchrotron research in every area of cancer – from developing a better understanding of how cancer cells work to delivering new cancer therapies.
Despite major advances in diagnosis and treatment, cancer still claims the lives of 8.8 million people every year around the world. About 4 million of these die prematurely (under the age of 70). World Cancer Day aims to raise the awareness of cancer and its treatment around the world. With the tagline ‘We can. I can.’, World Cancer Day is exploring how everyone can play their part in reducing the global burden of cancer.

Diamond has published over 900 publications in the last 12 months, with around 10% of these focusing on cancer. The wide-ranging research currently covers at least 12 cancer types, with many more general studies on the structure of cancer cells and pathways, potential drug targets and possible drug candidates. Building on last year’s review of some of the key studies in cancer that have taken place at Diamond, here is an update on studies that have been published in the last 12 months.

Modified antibody clarifies tumor-killing mechanisms

2018/01/262018/02/02

The structure of an antibody was modified to selectively activate a specific pathway of the immune system, demonstrating its value in killing tumor cells.

Immunotherapy—the use of the immune system to fight disease—has made tremendous progress in the fight against cancer. Antibodies such as immunoglobulin G (IgG) can identify and attack foreign or abnormal substances, including tumor cells. But to control and amplify this response, scientists need to know more about how elements of the immune system recognize tumor cells and trigger their destruction. There are two main pathways for this: antibody-dependent mechanisms and complement-dependent mechanisms.

The antibody pathway involves coating the surfaces of tumor cells with antibodies that recruit “natural killer” (NK) cells and macrophages (a type of white blood cell) to destroy the tumor cells. The complement pathway (so named because it complements the antibody pathway) also engages NK cells and macrophages and includes a third mechanism—a cascade of events culminating in tumor-cell destruction via a membrane attack complex (MAC).

>Read more on the ALS webpage

Image: extract of a schematic illustration (see on the ALS webpage)

Malaria in Action

2017/12/202018/01/15

Seeing the invisible

In 2007 Helen Saibil was at a conference in Australia. Amongst the presentations there happened to be talks on the parasites malaria and toxoplasma and how they infect mammalian cells, causing disease. Helen is a structural biologist and whilst listening she began to realise that her newly acquired skills -she was doing electron tomography of cells- might allow the researchers to see things they had never seen before.

Electron tomography reveals structures in the interiors of cells in great detail. What she hoped was that it could be used to look at the malaria parasites inside red blood cells [See images below] to get a better understanding of what they do there. Helen approached one of the speakers, Mike Blackman, then at the National Institute for Medical Research at Mill Hill in London, and so began a thriving collaboration. One that has produced the remarkable pictures of malaria parasites breaking out of infected human red blood cells on this page.

Helen Saibil and her colleagues used electron tomography to peer into malaria infected cells, looking at the parasites hiding and multiplying inside. The technique produces exquisitely detailed pictures able to reveal very tiny features, but it has one big drawback. Electrons cannot penetrate deep into the sample so it only works on very thinly sliced samples, much thinner than an individual cell. As a result it cannot be used to look at entire cells, or in this case red blood cells containing malaria parasites.