Tyler O'Neal, Staff Editor HEALTH

WPI awarded more than $900,000 to develop computational models for human cell division

Project funded by National Institutes of Health combines mathematics and biology to identify cellular forces to target cancer

Two researchers at Worcester Polytechnic Institute (WPI) have been awarded $917,999 by the National Institutes of Health to develop computational models for the study of a critical piece of cellular machinery that often goes awry in cancer.

The three-year study will use mathematical techniques and biological findings to assess how cellular forces influence the geometry of the mitotic spindle, a part of the cell’s machinery that is responsible for separating genetic material during cell division.

“There is too much going on during cell division to tease out and examine all the possible forces at work through laboratory experiments,” said Sarah Olson, WPI associate professor of mathematical sciences and the principal investigator (PI) of the project. “But by combining experiments with modeling, you can explore factors that lead to defective spindle structure in cells.” WPI professors Amity Manning (left) and Sarah Olson have teamed up to conduct cancer research.{module INSIDE STORY}

The study will build on previous work done by Olson and co-PI Amity Manning, assistant professor of biology and biotechnology, to build computational models to illuminate the forces in human epithelial cells during division. Both Olson and Manning are affiliated with WPI’s Bioinformatics and Computational Biology program.

Computational models use math and supercomputer simulations to adjust numerous variables in a complex system and observe outcomes. Cell division is a complex process in which a parent cell makes a copy of its chromosomes, which contain genetic instructions, and then splits into two new daughter cells.

A healthy cell undergoing division contains two centrosomes that anchor opposite ends of a molecular spindle. As the cell divides, one copy of all chromosomes is pulled toward each anchor point or spindle pole. Both cells that result from the division inherit an identical complement of chromosomes.

Cancer cells, however, often contain more than two centrosomes. The extra centrosomes must cluster together to form a functional spindle with two spindle poles so that a cancer cell can divide into two new cancer cells. If the extra centrosomes do not cluster together, a cancer cell with extra centrosomes divides into more than two new cells, each of which inherits too little genetic material to survive. This suggests that interventions that limit centrosome clustering could promote the death of cancer cells.

Researchers can watch cell division under microscopes, manipulate genes and proteins involved in the process, and monitor the consequences when defects occur, but there are limits to how much can be accomplished in laboratory experiments, Manning said.

“There is a lot of redundancy and overlapping functions in cell division,” Manning said. “We want to understand how centrosome clustering is regulated and how that influences basic cell biology. With modeling, we can simplify complex functions and test scenarios to better understand what’s happening.”

During the project, the researchers will develop new computational models and elucidate the relationship between initial centrosome positions in a cell and cell division. They also will identify how forces, such as the motor protein dynein, impact the movement of centrosomes in a dividing cell with extra centrosomes. Laboratory experiments will inform new computational models, Olson and Manning said, and the models will spur additional laboratory experiments.

“This is truly a collaborative project with a balance of math and biology,” Manning said. “We can brainstorm and think about modeling questions, biological questions, and how we can apply our expertise to this problem.”

Russian physicist develops software to measure black holes stability

Tyler O'Neal, Staff Editor HEALTH

Even if a black hole can be described with a mathematical model, it doesn't mean it exists in reality. Some theoretical models are unstable: though they can be used to run mathematical calculations, from the point of view of physics they make no sense. A physicist from RUDN University developed an approach to finding such instability regions. The work was published in the Physics of the Dark Universe journal.

The existence of black holes was first predicted by Einstein's general theory of relativity. These objects have so strong gravitational pull that nothing, not even light, can escape them. Dense and massive, black holes deform space-time (a physical construct with three spatial and one temporal dimension). Many mathematical models used to describe black holes include corrections to account for such space-time curvatures. The main condition of existence for every black hole model is its stability in cases of minor spatial or temporal changes. Mathematically unstable black holes make no physical sense, as the objects they describe cannot exist in reality. A physicist from RUDN University suggested a method to identify black hole instability parameters in 4D space-time. Even if a black hole can be described with a mathematical model, it doesn't mean it exists in reality. Some theoretical models are unstable: though they can be used to run mathematical calculations, from the point of view of physics they make no sense. A physicist from RUDN University developed an approach to finding such instability regions.{module INSIDE STORY}

"For a model to be considered feasible, a black hole described by it has to remain stable in case of minor space-time fluctuations. One of the most promising approaches to developing alternative gravity theories includes adding corrections to Einstein's equation, including the fourth-order Gauss-Bonnet correction and the Lovelock correction that provides a higher level of generalization," said Roman Konoplya, a researcher at the Educational and Research Institute of Gravitation and Cosmology, RUDN University.

The physicist studied stability in the Einstein-Gauss-Bonnet theory in which a black hole is described by Einstein's equation with a fourth additional component. Previously, he had focused on a different mathematical description of a black hole, the so-called Lovelock theory, that describes a black hole as a sum of an infinite number of components. The instability region turned out to be closely associated with the values of the so-called coupling constants: numerical coefficients by which the corrections to Einstein's equation are multiplied.

According to the physicist, the Einstein-Gauss-Bonnet model does not provide for the existence of small black holes, because if coupling constants are relatively big compared to other parameters (such as the radius of a black hole), the model almost always turns out to be unstable. The stability region is much bigger if the coupling constant has a negative value. Based on these calculations, he and his team developed a program to calculate black hole stability based on any of its parameters.

"Our approach helps test black hole models for stability. We made the code publicly available so that any of our colleagues could use it to calculate instability regions for models with an unspecified set of parameters," added Roman Konoplya.

Europe takes center-stage in global spread of the coronavirus

Tyler O'Neal, Staff Editor HEALTH

A collaboration between genome researchers at the UK's University of Huddersfield and Portugal's University of Minho, has led to one of the largest analyses of its kind focussing on thousands of virus genomes sampled from all around the world

University of Huddersfield's Archaeogenetics Research Group has mapped out the dispersal of the SARS-CoV-2 coronavirus, responsible for the current worldwide COVID-19 pandemic, putting Europe center-stage as the main source of the spread.

The group's findings, recently published in a special issue of the peer-reviewed journal Microorganisms, confirm that the virus originated in China and most likely jumped into humans from horseshoe bats. But that it is Europe, not China, which has been the main source for spreading the disease around the world.

The research also suggests that travel restrictions across Britain and Europe seem to have been too little and too late and that the actual spread of the virus to America and other parts of the world was large via Europe, and not directly from China. A collaboration between genome researchers at the University of Huddersfield and geneticists at the University of Minho in Portugal has discovered it is Europe, not China, which has been the main source of spreading the coronavirus disease around the world.{module INSIDE STORY}

The study focused on 27,000 virus genomes, sampled from all around the world. The researchers usually work on tracking ancient human migrations using mitochondrial DNA, and they capitalized on the fact that the virus genome is similar in crucial respects.

Still, the mammoth size of the database, even back in May when the study began, makes this one of the biggest analyses of its kind ever undertaken.

The intensive data analyses were carried out by clinical geneticist Dr. Teresa Rito and evolutionary geneticist Dr. Pedro Soares. Both are based at the University of Minho, in Portugal and have worked closely with the University of Huddersfield's Professor Martin Richards and Dr. Maria Pala, as part of the Archaeogenetics Research Group, on many occasions. The pair called upon the knowledge and expertise of their colleagues in the UK to help make sense of the data and publish their conclusions in double-quick time.

Professor Richards explained how there is a huge ongoing worldwide effort to understand the spread of the coronavirus and that researchers are trying to make their work available to the public as fast as possible.

As the world continues to face a rapidly spreading pathogen, Dr. Pala believes a greater understanding of the virus will better inform and improve upon policies designed to control the spread.

"With thousands of lives still at risk," added Dr. Pala, "the need for scientific research is now more crucial than ever."