Simulating cell infection by flu virus

Most people recover from the flu after a week or so, but the virus also causes many deaths each year. Peter Kasson is using molecular biology tools and advanced data models to gain an understanding at atomic level of how the influenza virus infects the cells in our body. This knowledge may lead to new treatments.

Peter Kasson

MD/PhD

Wallenberg Academy Fellow 2015

Institution:
Uppsala University

Research field:
Combining molecular understanding of the influenza virus with computer modeling of cell infection mechanisms

“Even though influenza has been studied for a long time, fundamental mysteries about the disease remain,” says Peter Kasson.

He has recently moved from the University of Virginia in the U.S. to Uppsala University, and his office and lab are not in order yet. Instead we meet in SciLifeLab´s social area.

“Influenza is a very interesting subject for research, because so many people catch it every year. Sometimes the virus also causes global pandemics and many deaths.”

With the support of the Knut and Alice Wallenberg Foundation he now aims to advance his research on the influenza virus in particular, although his work also concerns the zika virus, bacteria and drug resistance.

“The common denominator in my research is molecular physiological processes and infectious diseases.”

Seeing viral infections in real time

Just like our cells, the influenza virus has a membrane, Kasson explains. The details of the infection process, i.e. how the virus molecules enter the cell, involve these two membranes, and some proteins that modify the membrane.

“The molecular details of these processes are minute, no more than a hundred nanometers. There are also many molecules, which are not ordered in a regular shape, and they have moving parts. All this contributes to making the influenza virus so hard to study.”

Fortunately, major technological advances in recent years have given researchers sharper tools. In particular, Kasson is using fluorescence microscopy, which enables researchers to see what happens to a single virus in real time, as well as complex computer simulations of each atom in the infection process.

“By putting together experimental data describing the dynamics and structure of the virus, we can use simulations to predict behaviors in individual virus cells. But it is a major challenge to simulate something that only measures a few nanometers, and only takes place for a few microseconds.”

In addition to this delicate task, Kasson is looking forward to trying out some more advanced learning techniques to test his computer models.

“I want to see what happens if we push the virus and change some parts to make it work less well – can we then explain what happens. It’s going to be really fun.”

Simulated HIV at high school

The first time Kasson made a computer simulation of a virus was at high school in North Carolina, U.S.

“I was really interested in computers, and my uncle, who is a talented computer engineer, said ‘if I were starting my career now, I would go for biology’. So I created simple simulations of the HIV virus and its interaction with the immune system.  I was fortunate enough to receive mentorship from a professor at Duke University.”

And so his future was mapped out. Dr. Kasson studied computer science and biology at Stanford University, eventually gaining a combined MD and PhD. His medical background is an asset in his research, even though he does not actually meet patients.

“It’s an advantage to speak the same language as doctors, and important in understanding what a difference it makes to patients if I solve a specific problem.”

Interdisciplinary team

After a spell as a postdoc at Stanford Kasson began research at the University of Virginia. For two years he also commuted to Google’s headquarters in Silicon Valley, where he was a guest professor, with access to a large amount of computer time to carry out his simulations.

Dr. Kasson’s research involves biophysical experiments as well as complicated computer simulations. This requires an interdisciplinary research team. At present the researchers are dispersed between the University of Virginia, Boston, and Stanford. He also has access to both national and international computer resources.

A fair amount of traveling is needed to co-ordinate the work, but as soon as the laboratory is ready, he is excited to grow his base in Uppsala.

“It takes time and patience to set things up in a new environment and a new country – you often need to deal with the unexpected. But it’s exciting too. The most enjoyable aspect is coming into contact with new people, new ideas and new opportunities.”

“The support offered by the Knut and Alice Wallenberg Foundation for long-term basic research really is fantastic. The grant will allow us to follow the science wherever it goes, which is what makes projects like this one so attractive to researchers like me.”

Aiming for the membrane

Vaccines save many lives, but in a single infected person there will be hundreds of different mutant viruses. This makes it difficult to develop treatments. But research in this field is making progress. Among other things, antibodies are being developed that target the virus’ common parts, as Dr. Kasson explains:

“Most vaccines and drugs target the protein protruding from the membrane. There are other medicines, developed for other diseases that can alter the membrane itself. We are trying to gain a better understanding of this mechanism, and how it impacts the influenza infection process. We hope that our knowledge will contribute to more specific and powerful drugs to treat influenza in the future.”

Text Susanne Rosén
Translation Maxwell Arding
Photo Magnus Bergström