BioEngineering

Computational & Integrative Bioengineering

Contents

 

Faculty

Core Faculty

Other Faculty: see below.

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Description

Computational and Integrative Bioengineering is playing an increasingly central role in the Department. This thrust provides an integrated, quantitative framework for research within the department. At the core of this thrust area is the belief that use of computational methods to solve outstanding biological and pathophysiological problems fosters exchanges among different bioengineering thrusts and research areas. The mission statement of the faculty involved is to quantify, understand, predict and control the behavior of biological systems. Our goal is to produce the future thought leaders in Computational and Integrative Bioengineering.

The departmental thrust area in Computational and Integrative Bioengineering is designed to train students to become facile with rigorous experimental design and the testing of results with sophisticated quantitative analysis as a part of their disciplinary activity in pursuing careers in biosystems, biotransport, biomechanics, biosignals, biochemical and metabolic engineering and control analysis as applied to the biological and medical sciences, including physiology, pharmacology, medicine, biochemistry, medical imaging and related fields. The program is centered on developing a knowledge base in the mathematical, computational, physico-chemical and physiological or biochemical underpinnings of the biological topics under study. The training provides a set of intellectual tools for describing and understanding integrated sets of phenomena related to the individual student's experimental and practical focus.

The course work shall include components from three general areas:

  1. the biological sciences from cell and molecular biology all the way through to systems biology and physiology,
  2. engineering mathematics, modeling and simulation analysis, and data analysis using models, and
  3. other courses in engineering, mathematics, computer science and biological science (including biomechanics, signals, bioinstrumentation and biosensors) that provide additional breadth to the base of knowledge.

The student's choices of course credits in these three areas should emphasize courses in areas not learned in earlier studies at the undergraduate or graduate level, the objective being to achieve a balanced expertise in the biological and physical and engineering sciences.

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Areas of Research in Computational & Integrative Bioengineering at UW

The projects described below are subject to change without notice. To confirm whether or not a project is still underway, please contact the pertinent researcher(s).

In this field, there is a rapidly expanding need for bioengineers trained in the broad aspects of systems biology, from genomic expression and its regulation through to understanding and mathematical description of biochemical and physiological dynamics of endocrine or organ systems in health and disease, all the way through statistical models of disease progression and therapy. Research in these topics is eminently collaborative. Selected examples include:

Modeling software engineering and biosystem modeling languages.

This area of research involves the development of simulation analysis technologies and interfaces using XML and Java for web-based operation and in international collaborations. This is part of the mission of our research centers, the Resource Facility for Population Kinetics (RFPK) and the National Simulation Resource for Mass Transport and Exchange (NSR). This research is coordinated by Paolo Vicini at RFPK and Jim Bassingthwaighte at NSR. Specific modeling tools under development include JSIM, a Java-based, integrative model simulation and analysis environment, and SPK, the System for Population Kinetics. Other than software development and data analysis, projects under way in these include a broad diversity of investigative collaborations, both within the University and with investigators at other universities and institutes in the U.S. and abroad.

The Physiome Project

The Physiome Project, a large scale multi-institutional effort to provide a framework for the databasing and quantitative integrative analysis of information on the functional state of living organisms, provides a background for our other research programs. Its long-term goals are the quantitative understanding of the functioning of each organism, from E.coli to Homo sapiens, expressed at a varied level of depth in qualitative and quantitative models and databases. These can be used for teaching, research, clinical practice, guidance in therapy (genomic, pharmacologic, or surgical), and research for therapy in the pharmaceutical industry and the medical device industry. The coordinator for the Physiome Project at the UW is Jim Bassingthwaighte.

Quantitative image analysis

There are several projects within this area. One involves the magnetic resonance imaging (MRI) analysis of neovasculature volume in carotid atherosclerotic plaque. Neovasculature within atherosclerotic plaques is believed to be associated with infiltration of inflammatory cells and plaque destabilization. An imaging tool capable of measuring the extent of plaque neovasculature could be invaluable for identifying high-risk plaques or assessing the response to plaque-stabilizing therapies. Contrast-enhanced (CE) MRI has been used in numerous studies to investigate vascularity of tumors. The aim of this project is to develop analysis tools to determine whether the amount of neovasculature present in advanced carotid plaques can be non-invasively measured by dynamic contrast-enhanced MRI. This project is a collaboration between Paolo Vicini and the Vascular Imaging Laboratory directed by Chun Yuan and William Kerwin (Radiology, UW). Another project is centered on the development of analysis software for automated high-throughput tracking of axon growth. During embryonic development, neurons must project their axons along specific, predetermined paths in order to make precise connections with their synaptic targets. Gradients of chemotactic signaling molecules released by specialized cells create a chemical "roadmap" which the axon uses to navigate its way through the embryo. The process of axon guidance is highly complex due to the dynamic spatial and temporal expression of signaling molecules, the sensitivity of specific neuronal cell types to unique sets of signaling molecules. This research is a collaboration between Paolo Vicini and Albert Folch.

Molecular motion

There is considerable interest in the study of the chemo-mechanics, kinetics and regulation of motor and signaling proteins at the level of protein-protein interactions, and at the cellular and systemic levels. Diseases such as hypertrophic cardiomyopathy, hypothyroidism, diabetes and heart failure involve alterations in regulatory and contractile proteins that compromise cardiac output during normal activity or during strenuous activity. Designing new biomedical approaches to therapeutic interventions in heart disease (the #1 killer in the US) would be greatly aided by detailed understanding of the complex interactions between cardiac thin filament regulatory proteins and thick filament myosin motor proteins. Interpretation of experimental findings from study at all levels of organization, from isolated motors to integrative systems, are greatly aided by the development of analytical models. This research is conducted by Michael Regnier in collaboration with Martin Kushmerick, and Paolo Vicini.

Kinetic models of energetics of cells and organs in vivo

The overall theme of this area is the signaling, regulation and interaction of molecular and cellular mechanisms in metabolism to sustain and restore energy balance in muscle. Regulation of mitochondrial oxidative phosphorylation and of creatine kinase activity in transient and steady-state perturbations of chemical and mechanical power are major topics. Our interests cover the range of organization from single isolated animal muscles to intact human limb muscle, combining a reductionist tactic with a systems physiology approach. Part of the work entails constructing mathematical descriptions of each component and solving the system to compare with actual physiological performance measures. A part of our effort is directed to the study of human muscle function, and there are also opportunities to advance our understanding of the pathogenesis of selected disease processes while testing basic mechanisms. This research is conducted by Martin Kushmerick in collaboration with Paolo Vicini and Kevin Conley.

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Career Opportunities in Computational & Integrative Bioengineering

Graduates are in great demand now from academia and even more from industry. There is great need for quantitative analysis and integration of knowledge emerging from the giant strides made at the level of the genome and the proteome, in order to predict and understand both phenotype and the functioning of the organism. The pharmaceutical and device industries are experiencing an increased demand for efficiency in research and in development of drugs, implantable tissues and devices. They seek graduates with backgrounds in computational and integrative bioengineering to enhance their ability to predict the efficacy of drugs and the biocompatability of engineered tissues and devices. New companies are emerging in the field of systems and computational biology focusing on particular diseases, including genetic, acquired, and infectious diseases. Systems analysis, feedback and control systems, and operational analysis are important for any planning and designing of large projects.

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Degree Programs

Course credit requirements for MS and PhD degrees are those listed for the department (see also below). These will be more or less evenly spread among bioengineering courses, engineering courses offered by other departments, and biological courses offered by other departments. Bioengineering courses will aim at conveying in detail some specific areas of research and expose the students to a variety of state of the art, current enabling technologies (i.e. software and hardware; typically, more than one). The thesis and research topics might be in any area related to the expertise of the faculty, and will most likely be among currently funded research areas. Other programs on the UW campus in related areas are:

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Sample Programs

These programs fulfill the university and departmental requirements. Each is an actual program taken by a student within the past few years.

  1. PhD: Water and Solute Osmotic Exchange in the Heart
  2. PhD: Functional Parametric Images of Magnetic Resonance Imaging Studies
  3. MS: Modeling of Toxicokinetic Studies in Humans

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Subspecialty Areas & Suggested Coursework

The sample programs and suggested subspecialty areas that follow are meant as just as that. The samples of students' actual programs show you how some past students put together their programs. The course listings given below will assist you by suggesting what a particular program might target. The rule is that students should design their own programs, with care and deliberation, so that their advanced goals may be achieved. Choices should be made early in order to maximize the opportunities and minimize the duration of the overall program. The suggested graduation areas, or "specialty thrusts", may be regarded as a "minor" to the PhD program.

While the department requirements allow much flexibility, coherence in the program should be sought, with an eye to accomplishment in depth. In compliance with the most recent curriculum requirements of the department, students are required to fulfill a thrust requirement involving one in-depth sequence of 12 credits in the particular thrust area in which the student focuses. Five suggestions for fulfilling this requirement follow. While the student is not required to follow any of these, they provide a "minor" field of study in which the student could specialize. Five "minors" are being suggested: 1) bioengineering in drug development, 2) biotransport, 3) integrative biology, 4) biomechanics, 5) biomodeling methodology.

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Summary

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