Engineering Commons^™

Bacterial Chemotaxis Control Illustrates An Engineering Framework In The Creation Model, James D. Johansen

Proceedings of the International Conference on Creationism

This paper shows how biological design in bacteria chemotaxis control shows architectural design features that are found in many areas of biological life that reflect an engineering framework found in the creation model. The study highlights the bacteria chemotaxis control process utilizing the System Modeling Language (SysML) to leverage well-defined and proven engineering tools for architecting, analyzing, and refining complex systems. It first introduces SysML, and the advantages model-based systems engineering (MBSE) has for capturing system architecture and allowing for ongoing assessment of how biological system operates and the clarification of how much model detail is required to reveal a …

Serum Protein Signatures Using Aptamer-Based Proteomics For Minimal Change Disease And Membranous Nephropathy, Daniel A. Muruve, Hanna Debiec, Simon T. Dillon, Xuesong Gu, Emmanuelle Plaisier, Handan Can, Hasan H. Otu, Towia A. Libermann, Pierre Ronco

Department of Electrical and Computer Engineering: Faculty Publications

Introduction: Minimal change disease (MCD) and membranous nephropathy (MN) are glomerular diseases (glomerulonephritis [GN]) that present with the nephrotic syndrome. Although circulating PLA2R antibodies have been validated as a biomarker for MN, the diagnosis of MCD and PLA2R-negative MN still relies on the results of kidney biopsy or empirical corticosteroids in children. We aimed to identify serum protein biomarker signatures associated with MCD and MN pathogenesis using aptamer-based proteomics.

Methods: Quantitative SOMAscan proteomics was applied to the serum of adult patients with MCD (n = 15) and MN(n = 37) and healthy controls (n = …

Framework For The Evaluation Of Perturbations In The Systems Biology Landscape And Inter-Sample Similarity From Transcriptomic Datasets — A Digital Twin Perspective, Mariah Marie Hoffman

Dissertations and Theses

One approach to interrogating the complexities of human systems in their well-regulated and dysregulated states is through the use of digital twins. Digital twins are virtual representations of physical systems that are descriptive of an individual's state of health, an object fundamentally related to precision medicine. A key element for building a functional digital twin type for a disease or predicting the therapeutic efficacy of a potential treatment is harmonized, machine-parsable domain knowledge. Hypothesis-driven investigations are the gold standard for representing subsystems, but their results encompass a limited knowledge of the full biosystem. Multi-omics data is one rich source of …

Integration Of Neural Architecture Within A Finite Element Framework For Improved Neuromusculoskeletal Modeling, Victoria L. Volk, Landon D. Hamilton, Donald R. Hume, Kevin B. Shelburne, Clare K. Fitzpatrick

Mechanical and Biomedical Engineering Faculty Publications and Presentations

Neuromusculoskeletal (NMS) models can aid in studying the impacts of the nervous and musculoskeletal systems on one another. These computational models facilitate studies investigating mechanisms and treatment of musculoskeletal and neurodegenerative conditions. In this study, we present a predictive NMS model that uses an embedded neural architecture within a finite element (FE) framework to simulate muscle activation. A previously developed neuromuscular model of a motor neuron was embedded into a simple FE musculoskeletal model. Input stimulation profiles from literature were simulated in the FE NMS model to verify effective integration of the software platforms. Motor unit recruitment and rate coding …

Metabolic Network Analysis Of Filamentous Cyanobacteria, Daniel Alexis Norena-Caro

LSU Doctoral Dissertations

Cyanobacteria were the first organisms to use oxygenic photosynthesis, converting CO₂ into useful organic chemicals. However, the chemical industry has historically relied on fossil raw materials to produce organic precursors, which has contributed to global warming. Thus, cyanobacteria have emerged as sustainable stakeholders for biotechnological production. The filamentous cyanobacterium Anabaena sp. UTEX 2576 can metabolize multiple sources of Nitrogen and was studied as a platform for biotechnological production of high-value chemicals (i.e., pigments, antioxidants, vitamins and secondary metabolites). From a Chemical engineering perspective, the biomass generation in this organism was thoroughly studied by interpreting the cell as a microbial …

Metabolic Modeling Of Multispecies Microbial Biofilms, Poonam Phalak

Doctoral Dissertations

Biofilms are ubiquitous in medical, environmental, and engineered microbial systems. The majority of naturally occurring microbes grow as mixed species biofilms. These complicated biofilm consortia are comprised of many cell phenotypes with complex interactions and self-organized into three-dimensional structures. Approximately 2% of the US population suffers from non-healing chronic wounds infected by a combination of commensal and pathogenic bacteria whereas about 500,000 cases of Clostridium difficile infections (CDI) are reported annually. These polymicrobial infections are often resilient to antibiotic treatment due to the nutrient-rich environments and species interactions that promote community stability and robustness. This thesis focusses on developing metabolic …

Modeling The Interplay Between Photosynthesis, Co2 Fixation, And The Quinone Pool In A Purple Non-Sulfur Bacterium, Adil Alsiyabi

Department of Chemical and Biomolecular Engineering: Theses and Student Research

Rhodopseudomonas palustris CGA009 is a purple non-sulfur bacterium (PNSB) that can fix CO₂ and nitrogen or break down organic compounds for its carbon and nitrogen requirements. Light, inorganic, and organic compounds can all be used for its source of energy. Excess electrons produced during its metabolic processes can be exploited to produce hydrogen gas or biodegradable polyesters (polyhydroxybutyrate). A genome-scale metabolic model of the bacterium was reconstructed to study the interactions between photosynthesis, carbon dioxide fixation, and the redox state of the quinone pool. A comparison of model-predicted flux values with published in vivo MFA fluxes resulted in predicted …

Multiscale Spatio-Temporal Modeling Of Cell Population In Tissue Architecture And Drug Delivery Nanoparticles, Mohammad Aminul Islam

Doctoral Dissertations

"Multiscale nature of a biological system span at many order of magnitudes in time and space. Molecular interaction at lower scale is connected with the higher scale behavior of tissue or organism. Integrating the dynamics and information at different time and space can give a fundamental physiological understanding of the higher level phenomena. But complex features, functions, interconnectivity between different scales and lack of information on the fundamental physiological property make the model difficult and computationally challenging. The multiscale modeling approach can bridge the gap between different scale by a systemic integration of the complex dynamic behavior.

Here, the focus …

Spatiotemporal Modeling And Model Restructuration Approaches In Studies Of Intracellular Signalling Pathways, Md Shahinuzzaman

Doctoral Dissertations

"The main focus of the research is to understand the complex phenomena of cell transduction pathways and cell biology in a single cell. Mathematical modeling and experimental evaluation are widely used approaches for this kind of research. Firstly, A multiscale framework for protein-protein interaction has been established using Brownian dynamics algorithm. Sit specific feature, steric collision, diffusion, co-localization and complex formation with time and space has been included in this spatial modeling framework. By implementation of the time adaptive feature in this framework, the computation time reduces in an order of magnitude compared with traditional modeling framework. This multiscale Brownian …

Decoding Complexity In Metabolic Networks Using Integrated Mechanistic And Machine Learning Approaches, Tolutola Timothy Oyetunde

McKelvey School of Engineering Theses & Dissertations

How can we get living cells to do what we want? What do they actually ‘want’? What ‘rules’ do they observe? How can we better understand and manipulate them? Answers to fundamental research questions like these are critical to overcoming bottlenecks in metabolic engineering and optimizing heterologous pathways for synthetic biology applications. Unfortunately, biological systems are too complex to be completely described by physicochemical modeling alone.

In this research, I developed and applied integrated mechanistic and data-driven frameworks to help uncover the mysteries of cellular regulation and control. These tools provide a computational framework for seeking answers to pertinent biological …

Revelation Of Yin-Yang Balance In Microbial Cell Factories By Data Mining, Flux Modeling, And Metabolic Engineering, Gang Wu

McKelvey School of Engineering Theses & Dissertations

The long-held assumption of never-ending rapid growth in biotechnology and especially in synthetic biology has been recently questioned, due to lack of substantial return of investment. One of the main reasons for failures in synthetic biology and metabolic engineering is the metabolic burdens that result in resource losses. Metabolic burden is defined as the portion of a host cells resources either energy molecules (e.g., NADH, NADPH and ATP) or carbon building blocks (e.g., amino acids) that is used to maintain the engineered components (e.g., pathways). As a result, the effectiveness of synthetic biology tools heavily dependents on cell capability to …

A Community Genome-Scale Model Of Chinese Hamster Ovary Cell Metabolism Identifies Differences In The Efficiency Of Resource Utilization For Various Bioprocesses, Hooman Hefzi

Cell Culture Engineering XV

Genome-scale models of metabolism have successfully been employed in many microbial and eukaryotic metabolic engineering efforts by guiding pathway engineering and media optimization. They have also been used to explore the genotype-phenotype relationship in mammalian cells. The publication of the genomic sequence for Chinese hamster ovary (CHO) cells has allowed generation of genome-scale metabolic models (GeMs) for this organism. Here we have developed a high-quality community CHO GeM via careful reconciliation and manual curation of three independently developed CHO GeMs. This metabolic model, consisting of over 4000 metabolites and 6000 reactions, is capable of integrating proteomic, transcriptomic, and metabolomic data …

Predictive Engineering Of Cho Cells Using Systems Biology Models, Nathan Lewis

Cell Culture Engineering XV

Decades of bioprocess optimization have resulted in substantial improvements in recombinant protein production. However, some proteins remain difficult to express, and there is an increasing awareness of the need for improved control of critical quality attributes of recombinant protein drugs. To enable cell engineering efforts to enhance protein production and control product quality, we have enumerated the CHO cell parts through genome sequencing efforts,^1,2 and are now providing context to these parts by reconstructing genome-scale networks of the secretory pathway, glycosylation, and metabolism CHO (Figure 1). Using these models, which account for the activities of more than 2000 genes, …

Is Metabolism Goal-Directed? Investigating The Validity Of Modeling Biological Systems With Cybernetic Control Via Omic Data, Frank T. Devilbiss

Open Access Dissertations

Cybernetic models are uniquely juxtaposed to other metabolic modeling frameworks in that they describe the time-dependent regulation of cellular reactions in terms of dynamic "metabolic goals." This approach contrasts starkly with purely mechanistic descriptions of metabolic regulation which seek to explain metabolic processes in high resolution — a clearly daunting undertaking. Over a span of three decades, cybernetic models have been used to predict metabolic phenomena ranging from resource consumption in mixed-substrate environments to intracellular reaction fluxes of intricate metabolic networks. While the cybernetic approach has been validated in its utility for the prediction of metabolic phenomena, its central feature, …

Advancing Multiple Model-Based Control Of Complex Biological Systems: Applications In T Cell Biology, Jeffrey P. Perley

Open Access Dissertations

Activated CD4+ T cells are important regulators of the adaptive immune response against invading pathogens and cancerous host cells. The process of activation is mediated by the T cell receptor and a vast network of intracellular signal transduction pathways, which recognize and interpret antigenic signals to determine the cell's response. The critical role of these early signaling events in normal cell function and the pathogenesis of disease ultimately make them attractive therapeutic targets for numerous autoimmune diseases and cancers.

Scientists increasingly rely on predictive mathematical models and control-theoretic tools to design effective strategies to manipulate cellular processes for the advancement …

Systems Biology Of The Functional And Dysfunctional Endothelium, Jennifer Frueh, Nataly Maimari, Takayuki Homma, Sandra M. Bovens, Ryan M. Pedrigi, Leila Towhidi, Rob Krams

Department of Mechanical and Materials Engineering: Faculty Publications

This review provides an overview of the effect of blood flow on endothelial cell (EC) signalling pathways, applying microarray technologies to cultured cells, and in vivo studies of normal and atherosclerotic animals. It is found that in cultured ECs, 5–10% of genes are up- or down-regulated in response to fluid flow, whereas only 3–6% of genes are regulated by varying levels of fluid flow. Of all genes, 90%are regulated by the steady part of fluid flow and 10% by pulsatile components. The associated gene profiles show high variability from experiment to experiment depending on experimental conditions, and importantly, the bioinformatical …

Hyperglycemia Induces Differential Change In Oxidative Stress At Gene Expression And Functional Levels In Huvec And Hmvec, Hemang Patel, Juan Chen, Kumuda C. Das, Mahendra Kavdia

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Endothelial dysfunction precedes pathogenesis of vascular complications in diabetes. In recent years, the mechanisms of endothelial dysfunction were investigated to outline strategies for its treatment. However, the therapies for dysfunctional endothelium resulted in multiple clinical trial failures and remain elusive. There is a need for defining hyperglycemia-induced endothelial dysfunction with both generic and specific dysfunctional changes in endothelial cells (EC) using a systems approach. In this study, we investigated hyperglycemia-induced endothelial dysfunction in HUVEC and HMVEC. We investigated hyperglycemia-induced functional changes (superoxide (O₂‾), and hydrogen peroxide (H₂O₂) production and mitochondrial membrane polarization) …

Predictive Mathematical Model For Polyhydroxybutyrate Synthesis In Escherichia Coli, Angela Dixon

Engineering Datasets

Polyhydroxybutyrate has been studied as a potential biodegradable replacement for petrochemical plastics. Polyhydroxybutyrate synthesis is not native to Escherichia coli, but the genes have successfully been inserted through plasmids. However, polyhydroxybutyrate production needs to be more cost-effective before it can be commercially produced. A mathematical model for polyhydroxybutyrate synthesis was developed to identify genes that could be altered to increase polyhydroxybutyrate production. The major metabolic pathways included in the model were glycolysis, acetyl coenzyme-A synthesis, tricarboxylic acid cycle, glyoxylate bypass, and polyhydroxybutyrate synthesis. Reactions were modeled using kinetic mechanisms identified for each enzyme. The transcriptional network was incorporated into the …

Model-Guided Systems Metabolic Engineering Of Clostridium Thermocellum, Christopher Gowen

Theses and Dissertations

Metabolic engineering of microorganisms for chemical production involves the coordination of regulatory, kinetic, and thermodynamic parameters within the context of the entire network, as well as the careful allocation of energetic and structural resources such as ATP, redox potential, and amino acids. The exponential progression of “omics” technologies over the past few decades has transformed our ability to understand these network interactions by generating enormous amounts of data about cell behavior. The great challenge of the new biological era is in processing, integrating, and rationally interpreting all of this information, leading to testable hypotheses. In silico metabolic reconstructions are versatile …

Handling External Events Efficiently In Gillespie's Stochastic Simulation Algorithm, Brad Geltz

Theses and Dissertations

Gillespie's Stochastic Simulation Algorithm (SSA) provides an elegant simulation approach for simulating models composed of coupled chemical reactions. Although this approach can be used to describe a wide variety biological, chemical, and ecological systems, often systems have external behaviors that are difficult or impossible to characterize using chemical reactions alone. This work extends the applicability of the SSA by adding mechanisms for the inclusion of external events and external triggers. We define events as changes that occur in the system at a specified time while triggers are defined as changes that occur to the system when a particular condition is …