Neuroendocrine feedback system modeling & simulation

Integrated modeling and experimental laboratory research in neuroendocrinology has been a major focus of the Biocybernetics laboratory since 1972. Neuroendocrine physiology and hormone metabolism in the rat, sheep and several fishes have been studied experimentally in our labs – guided by simulation models – rats in the UCLA lab proper, sheep in Harbor General Hospital neuroendocrine laboratories, and fishes in laboratories of the Hawaii Institute of Marine biology and the University of Manitoba. Read More

Structural identifiability algorithms & software

The Biocybernetics laboratory has been making seminal contributions to the theory and practice of structural identifiability analysis since the early 1980s. Structural identifiability (SI) is the primary question, usually understood as knowing which unknown biomodel parameters are – and which are not – quantifiable in principle from particular input-output (I-O) biodata. Importantly, parameter identifiability problems can plague modelers during model quantification, even for relatively simple models. Read More

Tumor-supressor p53 signaling modeling

The p53 signaling system is one of the most important and studied control systems in cellular biology and its detailed structure is still very much in discovery mode. It’s known to be dysfunctional in most forms of cancer and this has been a major factor motivating numerous modeling efforts – generating a variety of different candidate structures as alternative mechanistic hypotheses – all directed toward better understanding of this system. Read More

THYROSIM Model Enhancements

The range of applicability of the model upon which THYROSIM is based is currently hypothyroid to mildly hyperthyroid. Students in the lab are currently working on extending this range to super-hyperthyroid and thyrotoxic conditions.  The subsystem models of the nonlinear enzymatic pathways responsible for converting thyroxine to triiodothyronine in tissues have been updated and are being validated. The simulator app will be updated with this new model during 2017.  Another version of THYROSIM – for individualized patient dosing – is also under development.

Alternative Model distinguishability algorithms & the software app DISTING

The model indistinguishability problem addresses whether there are other structured models within the same class (e.g. compartmental models), but with different structures, that fit given input-output (I-O) data equally well.  Establishing model uniqueness – or model disambiguation – is a major multifaceted problem in quantitative science, with methods and solutions available only for  very limited classes of structured models. Read More 

Manganism PBPK Modeling

In humans, inhaled manganese (Mn) can initiate neurodegeneration in the striatum – a tiny midbrain structure – and produce manganism, a disorder phenotypically mimetic of Parkinson’s disease. It was not completely clear how Mn has this effect, nor how much inhaled Mn gets to the striatum and by what routes. We developed a hybrid physiologically-based-multicompartmental model for manganese distribution dynamics and quantified it from published rat data to address this problem, as illustrated at the URL above and in Pamela Douglas’s publication cited above. Read More