Systems Biology

The term “systems biology” means different things to different people, but there is consensus that it involves considering how the components of biological systems and their interactions underlie the behaviour of the systems as a whole. A central part of systems biology is computation because the contribution and interplay between all of the components of complex biological systems cannot be fully understood by the human brain. Mathematical models running in computers are therefore the only way of combining the entire vast amount of scientific information in a way that allows its representation and analysis, and therefore allows its understanding.

As drug discovery has moved towards the rational design of drugs based on a mechanistic understanding of biology, it is clear that adopting a systems biology approach to drug discovery is logical. Physiomics’ clients enjoy a number of benefits:

• Benefit 1: Improvement in understanding of diseases and MOA

An understanding of the systems level can in turn provide explanations for the molecular basis of disease or the "Mechanism of Action" (MOA) of a drug. At Physiomics we generate mathematical models that allow our clients to observe the system dynamics and to interrogate the system with defined questions. Our models can therefore provide mechanistic insight into the results of clients’ wet-lab experiments.

• Benefit 2: Increased efficiency of research effort

Through an improved understanding of the biology of the system our clients can design better experiments to provide more definitive answers to the questions being asked. Furthermore, Physiomics’ models allow the user to perform experiments in silico rather than at the bench to critically test hypotheses. For example, our models can predict the effect of perturbing the system with hypothetical drugs, allowing different potential drug targets to be explored. As a result, our clients quickly determine which lines of investigation to pursue and those which to avoid, resulting in a reduction in the number of dead-end (and profitless) investigations.

• Benefit 3: Reduced cost

Physiomics’ models allow our clients to perform experiments in silico at a fraction of the cost of those performed through wet-lab experimentation. Moreover, as experiments performed in silico are much less time-consuming, drug development times and time-to-market are significantly reduced.

• Benefit 4: Support of key decision making

The Physiomics approach and technology can support decisions made throughout the whole drug discovery process. Areas where Physiomics can support decisions include:

• Target ranking – support “go” or “no-go” decisions for different possible drug targets;
• Compound ranking – support “go” or “no-go” decisions on specific alternative drug candidates for a specific target;
• Combination therapy – support decisions for potential combinations of developmental and existing drugs, or drugs with activity at multiple targets;
• Suggestions for potential molecular biomarkers of disease progression and therapeutic efficacy;
• Suggestions for optimal treatment regimes and combination strategies for individual cancer types;
• Provide Mechanism of Action for laboratory results that can be used to support patent applications and to gain regulatory approval.

Ultimately, integrating systems biology with the drug discovery process will reduce development times and result in drugs with enhanced efficacy and reduced side effects.

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