Dr. Laubenbacher is joining us from the University of Connecticut. He will be starting a Systems Medicine Laboratory here at the University of Florida. Dr. Laubenbacher is bringing with him a team of highly qualified individuals to collaborate in research.
The Laboratory for Systems Medicine strives to improve human health via the development of mathematical algorithms and innovative data science solutions. Some of our current projects include multiscale modeling of respiratory infections, multiscale modeling of ovarian cancer progression, developing tools for controlling bacterial growth of biofilms, and analysis of claims data.
Multiscale modeling of the battle over iron in invasive lung infection
Invasive aspergillosis is among the most common fungal infection in immunocompromised hosts and carries a poor outcome. The spores of the causative organism, Aspergillus fumigatus, are ubiquitously distributed in the environment. Healthy hosts clear the inhaled spores without developing disease, but individuals with impaired immunity are susceptible to a life-threatening respiratory infection that can then disseminate to other organs. The increasing use of immunosuppressive therapies in transplantation and cancer has dramatically increased suffering and death from this infection, and this trend is expected to continue. Current therapeutic approaches have been focused primarily on the pathogen, but a better understanding of the components of host defense in this infection may lead to the development of new treatments against this infection, possibly in combination with antifungal drugs. Iron is essential to all living organisms, and restricting iron availability is a critical mechanism of antimicrobial host defense against many microorganisms; conversely, successful pathogens have evolved potent mechanisms for scavenging iron from the host. These mechanisms have the potential to be harnessed therapeutically, for example with drugs that enhance the host’s iron sequestration mechanisms. The overarching goal of this project is to develop a multi-scale mathematical model that can serve as a simulation tool of the role of iron in invasive aspergillosis. The model will integrate mechanisms at the molecular scale with tissue-level events and a whole-body scale capturing the role of the liver. The project brings an innovative approach to the study of this infection, and introduces innovative features to multiscale modeling through a novel modular software design that improves flexibility, reproducibility, and model sharing.
Modular design of multiscale models
Availability of biomedical data sets across spatial and temporal scales makes it possible to calibrate complex models that capture integrated processes from the molecular to the whole organism level. This complexity poses multiple challenges related to mathematical modeling, software design, validation, reproducibility, and extensibility. Visualization of model features and dynamics is a key factor in the usability of models by domain experts, such as experimental biologists and clinicians. The proposed project addresses these challenges in the context of the immune response to an important respiratory fungal infection. Its goal is to develop a novel modular approach to model architecture, using a recently introduced technology of lightweight virtual machines and our user-friendly open-source platform for creating complex modular models in a transparent fashion. A key benefit of software containers is that they can encompass the entire computational environment of a model, enabling unprecedented reproducibility of computational results. The overarching computational goal is to develop a novel approach to the modular design of multiscale models.
Control of biofilms
The project addresses an important biomedical problem: how to control biofilms formed by Candida albicans, a dimorphic fungus that is an important cause of both topical and systemic fungal infection in humans, in particular immunocompromised patients. It is responsible for 85-95% of all vaginal infections resulting in doctor visits. C. albicans biofilms also form on the surface of implantable medical devices, and are a major cause of nosocomial infections. In recent years, it has been recognized that interactions with bacterial species integrated into biofilms can affect C. albicans virulence and other properties, It is therefore important to understand the interactions of C. albicans with bacterial species, in particular metabolic interactions. The next step then is to understand and, ultimately, control how varying compositions of the different microbial species affect their metabolic state and their ability to form biofilms.
Laboratory of Systems Medicine Faculty and Staff:
Reinhard Laubenbacher – Professor of Medicine; Dean’s Chair for Systems Medicine
Luis Sordo Vieira – Research Assistant Professor
Cory Brunson – Research Assistant Professor
Henrique De Assis Lopes Ribeiro – Research Post Doc
Eric Mei – OPS Software Engineer
Yara Sraf – Graduate Assistant