Cell membrane proteins imaged in 3-D

Scientists used lanthanide-binding tags to image proteins at the level of a cell membrane, opening new doors for studies on health and medicine.

A team of scientists including researchers at the National Synchrotron Light Source II (NSLS-II)—a U.S. Department of Energy (DOE) Office of Science User Facility at DOE’s Brookhaven National Laboratory—have demonstrated a new technique for imaging proteins in 3-D with nanoscale resolution. Their work, published in the Journal of the American Chemical Society, enables researchers to identify the precise location of proteins within individual cells, reaching the resolution of the cell membrane and the smallest subcellular organelles.
“In the structural biology world, scientists use techniques like x-ray crystallography and cryo-electron microscopy to learn about the precise structure of proteins and infer their functions, but we don’t learn where they function in a cell,” said corresponding author and NSLS-II scientist Lisa Miller. “If you’re studying a particular disease, you need to know if a protein is functioning in the wrong place or not at all.”
The new technique developed by Miller and her colleagues is similar in style to traditional methods of fluorescence microscopy in biology, in which a molecule called green fluorescent protein (GFP) can be attached to other proteins to reveal their location. When GFP is exposed to UV or visible light, it fluoresces a bright green color, illuminating an otherwise “invisible” protein in the cell.

>Read more on the National Synchrotron Light Source II (NSLS-II) website

Image: Ultrabright x-rays revealed the concentration of erbium (yellow) and zinc (red) in a single E.coli cell expressing a lanthanide-binding tag and incubated with erbium.

Funding research crucial to Africa: Energy and healthcare

The 27th March 2019 saw the official launch of START (Synchrotron Techniques for African Research and Technology), a £3.7M grant awarded to a consortium of researchers led by Diamond Light Source by the Science and Technology Facilities Council (STFC) to work with African scientists on START.

Africa does not yet have a synchrotron light source, but African researchers are keen to apply synchrotron techniques to their research problems. The START project will fund research posts in Africa and the UK with a focus on two key areas crucial to development in Africa – energy and healthcare . The scientific results that come out of the project will be valuable in themselves, and may also lead to commercial applications, but START will also promote the development of research capabilities within Africa, and international research collaborations.

For Diamond Principal Investigator, Prof. Chris Nicklin, this will be the most important result: It is an exciting prospect to work together on these challenging problems and this funding will enable us to form very strong links at all levels, in particular helping to train the next generation of researchers in nations that have not had the chance to access and exploit synchrotron based techniques in their research. The work will focus around the development needs of African countries, driven by the Africa-based investigators and the non-government organisations (NGOs) that we have on board.

>Read more on the Diamond Light Source website

Biofortification of field-grown cassava

Micronutrient deficiency, sometimes called the “hidden hunger,” causes severe health problems in hundreds of millions of people worldwide, and is particularly damaging to children, in whom it can impair both physical and cognitive development.

Biofortification is one of the most promising tools available for alleviating this problem, but is a multifaceted challenge involving not only creating nutrient-rich crop varieties, but also ensuring bioavailability of these nutrients, protecting against increased uptake of toxins such as cadmium, and adoption by affected populations.

Image: X-ray Fluorescence images, obtained at CHESS, comparing localization of Fe, Zn, and Ca in the stems and storage roots of several genetically distinct varieties of Cassava; (from Narayanan et al, doi: 10.1038/s41587-018-0002-1). Scale bars: 1 mm.

Tungsten accumulation in bone raises health concerns

McGill University scientists have identified exposure to tungsten as problematic after they determined how and where high levels of the metal accumulate and remain in bone.

“Our research provides further evidence against the long-standing perception that tungsten is inert and non-toxic,” said Cassidy VanderSchee, a PhD student and a member of a McGill research group headed by chemistry professor Scott Bohle.

Tungsten is a hard metal with a high melting point and, when combined with other metals and used as an alloy, it’s also very flexible.

Because of these properties and under the assumption that tungsten is non-toxic, it has been tested for use in medical implants, including arterial stents and hip replacements, in radiation shields to protect tissue during radiation therapy, and in some drugs. Tungsten is found in ammunition as well as in tools used for machining and cutting other metals.

Tungsten also occurs naturally in groundwater where deposits of the mineral are found. Exposure to high levels of tungsten in drinking water in Fallon, Nevada, was investigated for a possible link with childhood leukemia in the early 2000s. This investigation lead scientists to question the long-held belief that exposure to tungsten is safe and prompted the Centers for Disease Control and Prevention in the U.S. to nominate tungsten for toxicology and carcinogenesis studies.

>Read more on the Canadian Light Source website

Image: Cassidy VenderSchee

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

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.

>Read more on the Australian Synchrotron website


Gold protein clusters could be used as environmental and health detectors

Peng Zhang and his collaborators study remarkable, tiny self-assembling clusters of gold and protein that glow a bold red. And they’re useful: protein-gold nanoclusters could be used to detect harmful metals in water or to identify cancer cells in the body.
“These structures are very exciting but are very, very hard to study. We tried many different tools, but none worked,” says Zhang, a Dalhousie University professor.

Peng Zhang and his collaborators study remarkable, tiny self-assembling clusters of gold and protein that glow a bold red. And they’re useful: protein-gold nanoclusters could be used to detect harmful metals in water or to identify cancer cells in the body.

“These structures are very exciting but are very, very hard to study. We tried many different tools, but none worked,” says Zhang, a Dalhousie University professor.

>Read more on the Canadian Light Source website

Image: The protein-gold structure. The protein, which both builds and holds in place the gold cluster, is shown in grey.

Investigation of metal deposition in organs after joint replacement

Synchrotron analysis shows potentially harmful metals from implants can find their way into human organs.

The hip replacement is considered to be one of the most successful orthopaedic interventions, with 75,000 performed each year by the NHS alone. However, the implants used to replace hips contain metals, such as chromium and cobalt, which are potentially toxic and which can be deposited into tissues around the implant site due to wear and corrosion. A team of researchers used X-ray absorption spectroscopy (XAS) on the I18 beamline to show that these metals can also find their way into organ tissues. Their results suggest that chronic diseases, such as diabetes, may create conditions in which mildly toxic trivalent chromium (CrIII) particles from replacement joints are reoxidised within the body to form carcinogenic hexavalent chromium (CrVI). Their results have been published in the Journal of Trace Elements in Medicine and Biology.

>Read more on the Diamond Light Source website

Image: Overview of the study (entire figure to see here).