Mathematics of Stem Cells

Cell populations are complex. Their collective functioning, turnover, and cooperation are at the basis of the life of multicellular organisms, such as humans. When this goes wrong, an unwanted evolutionary process can begin that leads to cancer. Mathematics cannot cure cancer, but it can be used to understand some of its aspects, which is an essential step in winning the battle.

How does cancer cope with genetic chaos?

When a cell divides, it needs to copy its entire genome accurately and make sure each of the two new daughter When a cell divides, it needs to copy its entire genome accurately and make sure each of the two new daughter cells receives a complete set of chromosomes. But cells can make mistakes, and bits of chromosomes can get swapped around, lost, or copied too often. This genetic chaos is called Chromosomal Instability. If there is too much chromosomal instability in a cell, signals by DNA-checking proteins cause the cell to self-destruct. But cancer cells seem to be able to accumulate chromosomal instability without self-destructing. This leads to a lot of genetic diversity in a tumour, making them hard to treat.

New research from Prof. Charles Swanton at the Francis Crick Institute and University College London sheds light on a number of ways cells can cope with this chromosomal instability. They have uncovered new cellular signalling pathways through which cancer cells can bypass the DNA-checking proteins that would otherwise cause the cell to self-destruct. They have also found that cancer cells take longer to divide than healthy cells, which gives them more time to fix the worst errors.

This means that cancer cells are constantly balancing the amount of chromosomal instability. If there isn’t a lot of genetic chaos, the cancer is easier to treat, and if there’s too much chaos, the cancer cells are too damaged to divide. Tumour evolution selects for the right amount of chromosomal instability that allows a tumour to keep growing.
But if we can upset the balance to either extreme, we might make a tumour more vulnerable to treatment.

DNA Nanotubes Build Bridge Between Two Molecular Posts

In a microscopic feat that resembled a high-wire circus act, Johns Hopkins researchers have coaxed DNA nanotubes to assemble themselves into bridge-like structures arched between two molecular landmarks on the surface of a lab dish. The team captured examples of this unusual nanoscale performance on video

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This self-assembling bridge process, which may someday be used to connect electronic medical devices to living cells, was reported by the team recently in the journal Nature Nanotechnology.

To describe this process, senior author Rebecca Schulman, an assistant professor of chemical and biomolecular engineering in the university’s Whiting School of Engineering, referred to a death-defying stunt shown in the movie “Man on Wire.” The film depicted Philippe Petit’s 1974 high-wire walk between the World Trade Center’s Twin Towers.

Schulman pointed out that the real-life crossing could not have been accomplished without a critical piece of old-fashioned engineering: Petit’s hidden partner used a bow and arrow to launch the wire across the chasm between the towers, allowing it to be secured to each structure.

“A feat like that was hard to do on a human scale,” Schulman said. “Could we ask molecules to do the same thing? Could we get molecules to build a ‘bridge’ between other molecules or landmarks on existing structures?”

The paper’s lead author, Abdul Mohammed, a postdoctoral fellow in Schulman’s lab, used another analogy to describe the molecular bridge-building feat they demonstrated at the nanoscale level. “If this process were to happen at the human scale,” Mohammed said, “it would be like one person casting a fishing line from one side of a football field and trying to hook a person standing on the other side.”

To accomplish this task, the researchers turned to DNA nanotubes. These microscopic building blocks, formed by short sequences of synthetic DNA, have become popular materials in the emerging nanotechnology construction field. The sequences are particularly useful because of their ability to assemble themselves into long, tube-like structures known as DNA nanotubes.

In the Johns Hopkins study, these building blocks attached themselves to separate molecular anchor posts, representing where the connecting bridge would begin and end. The segments formed two nanotube chains, each one extending away from its anchor post. Then, like spaghetti in a pot of boiling water, the lengthening nanotube chains wriggled about, exploring their surroundings in a random fashion. Eventually, this movement allowed the ends of the two separate nanotube strands to make contact with one another and snap together to form a single connecting bridge span.

To learn more about how this process occurs, the researchers used microscopes to watch the nanotubes link to their molecular landmarks, which were labeled with different coloured fluorescent dyes and attached to transparent glass. The team’s video equipment also captured the formation of nanotubes spans, as the two bridge segments lengthened and ultimately connected. Completion of the nanoscale bridge in the accompanying example took about six hours, but the team’s videos were sped up significantly to enable a more rapid review. Depending on how far apart the molecular anchor posts were located, the connection process took anywhere from several hours to two days.

The ability to assemble these bridges, the researchers say, suggests a new way to build medical devices that use wires, channels or other devices that could “plug in” to molecules on a cell’s surface. Such technologies could be used to understand nerve cell communication or to deliver therapeutics with unprecedented precision. Molecular bridge-building, the researchers said, is also a step toward building networked devices and “cities” at the nanoscale, enabling new components of a machine or factory to communicate with one another.

WPI’s Liquid Biopsy Chip Captures Cancer Cells in a Simple Blood Test

Cancers that spread from one organ to another can be difficult to treat, so it is best to catch them early. Since cancer cells spread through the bloodstream, a blood test that can capture and identify circulating tumor cells could be a life saver. A new technology developed at Worcester Polytechnic Institute (WPI) does just that. What’s more, it works quickly and is inexpensive to make, paving the way for a simple and routine cancer screening tool.

Light-based therapy for Alzheimer’s disease

Researchers in Li-Huei Tsai’s laboratory at the Picower Institute for Learning and Memory have shown that disrupted gamma waves in the brains of mice with Alzheimer’s disease can be corrected by a unique non-invasive technique using flickering light. (Learn more: http://news.mit.edu/2016/visual-stimu…)

Tsai Lab: http://tsailaboratory.mit.edu/