Cancer is a notoriously difficult disease to treat. Not only do a wide variety of cancers exist, requiring specialized treatments for each type, but cancer cells within an individual can morph and render previously potent therapeutics ineffective. Thus, there is a continual need to discover new, effective drugs. Research from Dr. Norihiko Nakazawa in the G0 Cell Unit at the Okinawa Institute of Science and Technology Graduate University (OIST) led by Prof. Mitsuhiro Yanagida, may help make the discovery process easier. This research was published in Genes to Cells.
Cancer cells differ from normal cells in a variety of different ways. Most notably, malignant cells exhibit a much higher rate of replication and proliferation than normal ones. The rapid growth of these cells can result in tumor formation and metastasis, or the spreading of cancer to other parts of the body. Fortunately, scientists have been able to exploit these properties to create new treatments. Since the proteins involved in DNA replication are considerably more active in cancer cells than in normal ones, researchers have discovered that drugs which target these proteins will disproportionately affect the malignant cells. These drugs are designed to only affect active proteins, so that even though the same proteins exist in normal cells, the majority of the normal cells will contain inactive proteins at the time of treatment, and thus be unaffected.
Dr. Nakazawa’s research centered on the use of a specific anti-cancer drug, ICRF-193, which targets a protein called DNA topoisomerase II. As part of his research, Dr. Nakazawa treated fission yeast with ICRF-193 and observed the effects. Typically, during cell reproduction, DNA is copied so that a cell temporarily contains twice the amount of DNA than it normally does. These two copies of chromosomal DNA are pulled to different ends of the cell by a protein structure called the mitotic spindle. Once the chromosomal DNA is separated, the cell begins to divide into two identical daughter cells.
When Dr. Nakazawa treated fission yeast with ICRF-193, he noticed that the cells appeared to have difficulty separating after DNA replication had occurred. Instead of separating normally, the mitotic spindle appeared to continue to lengthen despite failing to fully separate the two copies of DNA, producing an arched shape until eventually snapping in the middle. This “arched and snapped” appearance seemed to be unique to the ICRF-193 treated cells.
Researchers can utilize this “arched and snapped” appearance to look for other drugs that affect fission yeast proteins in the same manner. The replication machinery and DNA-bound proteins of fission yeast are highly conserved and thus remarkably similar to other organisms, including humans. Because of this similarity, drugs that affect these proteins in fission yeast are likely to affect the related highly active proteins in human cancers. This research makes it plausible to use fission yeast in the place of human cells in the discovery process of novel cancer drugs.
There are many disadvantages to using human cells in the initial stages of creating a new therapy. Scientists often have to test a large number of compounds in order to find one that is effective against a particular target. Human cells are costly to take care of and require a lot of time and specific conditions in order to grow. According to Dr. Nakazawa, “fission yeast is a relatively fast, easy to use model system that is low cost,” making it advantageous for use in drug screens. Time and cost are often major hurdles in the process of drug development, so any discoveries that expedite the process can help get the next cancer cure in the hands of patients sooner.
A team of physicists at the Okinawa Institute of Science and Technology Graduate University (OIST) has predicted the existence of a new kind of spin liquid. A spin liquid is an exotic phenomenon that intrigues scientists: it is a magnetic material in which the magnetism of the atoms fluctuates continuously between different directions. Their theoretical discovery found confirmation through computer simulation. Notably, this mathematical description of a spin liquid shares important similarities with a gauge symmetry, which is a key element in the way physics describes the world. The researchers, all from OIST Theory of Quantum Matter Unit, published their results in Nature Communications.
Spin liquids are well known to physicists. The name ‘spin liquid’ is misleading, as a spin liquid is a solid that is liquid only from the point of view of the directions of its atoms’ magnetism. The direction of an atom’s magnetism is defined by the magnetism that originates from the rotation of the electrons around the atom’s nucleus. In a visual representation of an atom, the magnetism’s direction can be drawn as an arrow, which points in a specific direction of space.
At high temperature, the arrows inside a given material typically point in random directions: the magnetism of each atom is different. When the material is cooled down, the arrows usually arrange themselves in a repeating pattern. A spin liquid is a specific type of magnetic material in which the atoms’ directions keep fluctuating even at low temperatures.
Spin liquids are hard to pin down because they lack the regular repeating patterns of other magnets. Being able to predict the existence of a new kind of spin liquid is then a very important achievement. The new spin liquid theoretically discovered by the scientists is characterized by a unique internal structure describing how the magnetism of each atom relates to the magnetism of those around it.
The finding is significant because there is a strong relationship between the scientists’ mathematical description of the spin liquid and a gauge symmetry. Gauge symmetries are the way in which physicists understand the fundamental forces of nature, such as electromagnetism. Finding gauge symmetries in spin liquids is interesting because it reveals deep connections between different branches of physics. These connections have historically fostered new understandings of how we interpret reality from the physicists’ point of view.
The Okinawa Institute of Science and Technology Graduate University (沖縄科学技術大学院大学 Okinawa Kagaku Gijutsu Daigakuin Daigaku?, OIST) is an interdisciplinary graduate school located in Onna, Okinawa Prefecture, Japan.
The school offers a 5-year PhD program in Science. Over half of the faculty and students are recruited from outside Japan, and all education and research is conducted entirely in English.
The university has no departments—OIST researchers conduct multi-disciplinary research in neuroscience, mathematical and computational sciences, physics, chemistry, integrative biology and molecular, cell, and developmental biology. The university received accreditation on November 1, 2011, and began classes in September 2012.
OIST relies on public subsidies paid by the Japanese government. The government subsidy for OIST comes in two areas: a subsidy for operations and a subsidy for facilities.
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