| RESEARCH HIGHLIGHTS |
and crystalline phases. In the crystalline phase, where Te and Fe atoms were strongly bonded in a regular lattice, electrons were engaged in strong hybridization, meaning their orbitals overlapped and caused their electrons to localize. Thus, lone-pair electrons were incor- porated as part of the integral structure.
In contrast, when FeTe entered its amor-
phous phase, some Te atoms were orientated so that their lone-pair electrons delocalized from the atoms, resulting in holes that acted as charge carriers. “We are hopeful that FeTe could prove to be useful material for phase-change memory,” says
Bai. “It could also act as an effective thermoe- lectric material, generating electric current in response to temperature.”
1. Ho, H. W., Branicio, P. S., Song, W. D., Bai, K., Tan, T. L. et al. Unravelling the anomalous electrical and optical phase-change characteristics in FeTe. Acta Materialia 112, 67–76 (2016).
Myeloproliferative neoplasms:
NOT ALL CHAPERONES ARE TO BE TRUSTED
Myeloproliferative neoplasms (MPNs) are blood cancers that cause the bone marrow to produce too many red or white blood cells, or platelets, leading to various complications. There is no known cure for most MPNs. In 2013, scientists discovered a link
between some forms of MPNs and mutations in a housekeeping gene known as CALR, which codes for calreticulin — a ‘chaperone molecule’ that promotes folding of proteins. Stefan Constantinescu of the Ludwig
Institute for Cancer Research in Belgium says the 2013 breakthrough was the first known
www.astar-research.com Vesicle
Mutant versions of the chaperone molecule calreticulin activate thrombopoietin receptor, which in turns activates the JAK2−STAT pathway.
Golgi apparatus
Endoplasmic reticulum
Nucleus
(MPL/TpoR), which regulates the production of blood platelets, in the process that drives some MPNs1
. The work involved an interna-
MUTANT VERSIONS OF A ‘HOUSEKEEPING GENE’ ARE SHOWN TO ACTIVATE A PATHWAY THAT LEADS TO OVERPRODUCTION OF CERTAIN KINDS OF BLOOD CELLS
example of a chaperone turning into an oncogenic activator of cell proliferation, but that molecular mechanisms underlying this connection were unknown. “To learn how to treat MPNs, we first
need to know what cell signaling or survival pathways are active in diseased cells,” explains Choong Meng Ling of the A*STAR Experi- mental Therapeutics Centre. Studies by Constantinescu, Ling and
co-workers have implicated an abnormal interaction between CALR mutants and the receptor for the hormone thrombopoietin
tional collaboration with Robert Kralovics's group, in Vienna, Austria and William Vainchenker's group in Villejuif, France. One of CALR’s roles is the folding and
processing of the thrombopoietin receptor before it is transported to the cell surface. The researchers discovered that the mutant CALRs incorrectly fold the thrombopoietin receptor into active receptors, both in the cell and at its surface. This persistently activates the JAK2−STAT pathway (see image), which the team had previously shown is activated in some MPNs. The scientists then employed a drug
combination study approach known as the Chou−Talalay method. “This approach allowed us to kill two birds with one stone: it helped us to simultaneously identify the cell survival pathways downstream of mutant CALRs and the drugs that could be used
A*STAR RESEARCH 5
© 2016 Christian Pecquet, LICR
Cell surface membrane
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