NIAID program reveals unique immune response insights
that uses computational systems biology to better understand the
biochemical networks that regulate the interactions between
infectious organisms and the human or animal cells they infect.
The use of this model is an attempt to better explain processes such as how infectious organisms invade human cells, how the toxins they produce cause cell and tissue destruction and how these pathogens evade or manipulate the immune response. This inevitably will lead to a more focused tailoring of drug therapies and treatments.
The Program in Systems Immunology and Infectious Disease Modelling (PSIIM), developed by the National Institute of Allergy and Infectious Diseases (NIAID), uses experimental approaches to determine how closely these simulations predict real behaviour.
As the models improve, scientists should gain the ability to predict how drugs and other interventions will affect a cell or organism and whether the host will tolerate such treatments while they fight the infectious agent.
Although most of the studies will be conducted with less dangerous pathogens, PSIIM scientists will also be able to examine microbes that cause diseases such as anthrax, virulent forms of influenza, tularemia and plague.
"Understanding the daunting complexity of biological systems is the greatest challenge and at the cutting-edge of science in the 21st century," commented NIH director Elias Zerhouni.
"The creation of this program will strengthen the intramural research program here on the NIH campus."
Central to the PSIIM research project is a software package called Simmune, which enables biologists to model many types of biological systems.
The software allows a scientist to use a simple graphical interface to easily define the interactions between individual molecules in a large network, or the behaviours of cells in response to external signals.
Once scientists input quantitative information obtained by laboratory measurements, Simmune can then simulate the behaviour of the whole signalling network or of an entire cell.
The software does this by automatically creating a mathematical model involving special equations and then solving these equations for the specific conditions the user entered into the program.
"Once we understand these interactions, we can make strategic decisions about how to interfere with infectious disease pathology or how to direct immune responses to better fight infections," said DIR Director Kathryn Zoon.
"These new insights can serve as the starting point for the design of new drugs to treat diseases or the development of new vaccines."
The wealth of information gleaned about the human genome in recent years has identified many of the genes, proteins and other molecules involved in various biological systems.
But understanding how these pieces work together to produce the complex physiological and pathological behaviour of cells and organisms is not well understood.
Before Simmune, making such mathematical models by hand often took months and required extensive expertise in applied mathematics.
In addition, making changes to an existing model was very time-consuming, which limited the complexity of what could be modelled.
With Simmune, we are trying to empower a broad range of biological experts, allowing them to easily make and modify detailed quantitative models of the biological systems they have studied in the lab for years.
"The hope is that these models will provide a deeper understanding of how complex behaviours arise, leading to new insights into disease," said Head of NIAIDs Division of Intramural Research (DIR), immunologist Ronald German.
