Biochemical and Biomolecular Engineering Commons^™

Utilizing Virtual High-Throughput Screens To Identify Promising Inhibitors Of Complement Factor C1s, Lyndsey Schmucker

Williams Honors College, Honors Research Projects

A large study was conducted to identify possible drug candidates to treat various diseases using computer algorithms, virtual high-throughput screens, and experimental validation of activity. Since the algorithm has the capability to screen millions of compounds, it is beneficial to pharmaceutical development as it allows a larger pool of compounds to be considered that would have otherwise been overlooked. As part of this larger study, this project attempts to identify drug candidates to treat human complement factor C1, a protein which causes tissue damage when underregulated¹. A series of designed experiments validate candidates and confirm the performance of …

A Framework For Heterologous Biosynthesis Of Natural Products In Mammalian Cells Via Polymer-Mediated Transfections, Logan Warriner

Theses and Dissertations--Chemical and Materials Engineering

With the promise to treat a multi-faceted list of serious inherited and acquired diseases, such as cancer, neurodegenerative and infectious diseases, and inherited genetic indications, gene therapy has continued to push the boundaries of traditional medicine since its earliest implementation. While much progress has been made, clinical success has largely remained elusive. Immunogenicity, difficulty producing commercially relevant quantities, and having a limited genetic payload still limits the ability of viruses to act as directed delivery agents for genetic material. As such, researchers have turned to cationic synthetic materials as a means of delivering nucleic acids, which can circumvent the immune …

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …

A Microfluidic Paper-Based Analytical Device For Early Diagnosis And Prognosis Of Acute Myocardial Infarction, Lim Wei Yin

Student Works (2020-2029)

Acute myocardial infarction (AMI), also termed as heart attack, is often clinically screened by blood test through the measurement of cardiac biomarkers (i.e., troponin (T or I), creatine kinase (CK−MB) and myoglobin) and electrocardiography (ECG) changes which are presented to the hospital. However, the early diagnosis of AMI is challenging because the detection of biomarkers such as troponin (T or I) and CK−MB are only reliable at the intermediate and later stages (> 6 hours after chest pain onset), during myocardial injury and myocardial infarction. On the other hand, myoglobin often been used as early biomarker which is detectable within …

Design And Development Of A Perfusion Bioreactor With Internal Volume Expansion And Cell Retention For Cell And Gene Therapy Manufacturing, Corinna Doris

KGI Theses and Dissertations

Economically producing patient-specific cell therapies at commercial levels remains a challenge as it requires manufacturing separate batches per patient where the production system must be scaled-out rather than scaled-up to supply more patient doses. The resulting high production cost and consequent price-point can limit patient access. Specifically, the current cell expansion processes are highly manual and laborious, with the number and complexity of operations and components increasing the opportunities for failure and contamination. This work therefore aims to design a mechanically simple bioreactor that is better suited for scale-out by consolidating the cell expansion process to fewer components, vessels, and …

A Review Of Materials For Managing Bone Loss In Revision Total Knee Arthroplasty, Romina Shafaghi, Omar Rodriguez, Emil H. Schemitsch, Paul Zalzal, Stephen D. Waldman, Marcello Papini, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

In 2014–2015, 61,421 total knee arthroplasties (TKAs) were performed in Canada; an increase of about 20% over 2000–2001. Revision total knee arthroplasties (rTKAs) accounted for 6.8% of TKAs performed between 2014 and 2015, and this is estimated to grow another 12% by 2025. rTKAs are typically more complicated than primary TKAs due to the significant loss of femoral and tibial bone stock. The escalating demand and limitations associated with total knee arthroplasty and their revision drives the development of novel treatments. A variety of materials have been utilized to facilitate regeneration of healthy bone around the site of a knee …

The Effect Of Tantalum Incorporation On The Physical And Chemical Properties Of Ternary Silicon–Calcium–Phosphorous Mesoporous Bioactive Glasses, Andrew Mendonca, Md Saidur Rahman, Adel Alhalawani, Omar Rodriguez, Reid C. Gallant, Heyu Ni, Owen M. Clarkin, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Synthesis and characterization of the first mesoporous bioactive glasses (MBGs) containing tantalum are reported here, along with their potential application as hemostats. Silica MBGs were synthesized using with the molar composition of (80-x)% Si, 15% Ca, 5% P, and x% Ta. It was found that incorporation of >1 mol % Ta into the MBGs changes their physical and chemical properties. Increasing Ta content from 0 to 10 mol % causes a decrease in the surface area and pore volume of ~20 and ~35%, respectively. This is due to the increase in nonbridging oxygens and mismatch of thermal expansion coefficient which …

Measurement Of Adhesion Of Sternal Wires To A Novel Bioactive Glass-Based Adhesive, Varinder Pal Singh Sidhu, Mark R. Towler, Marcello Papini

Chemical and Biochemical Engineering Faculty Research & Creative Works

Stainless steel wires are the standard method for sternal closure because of their strength and rigidity, the simplicity of the process, and the short healing time that results from their application. Despite this, problems still exist with sternal stability due to micromotion between the two halves of the dissected and wired sternum. Recently, a novel glass-based adhesive was developed which, in cadaveric trials and in conjunction with wiring, was shown to restrict this micromotion. However, in order to avoid complications during resternotomy, the adhesive should adhere only to the bone and not the sternal wire. In this study, sternal wires …

Bioactive Glass Fiber Fabrication Via A Combination Of Sol-Gel Process With Electro-Spinning Technique, Malvika Nagrath, Adel Alhalawani, Alireza Rahimnejad Yazdi, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

No abstract provided.

Bioengineering Extracellular Matrix Scaffolds For Volumetric Muscle Loss, Kevin Roberts

Graduate Theses and Dissertations

Volumetric muscle loss overwhelms skeletal muscle’s ordinarily capable regenerative machinery, resulting in fibrosis and severe functional deficits which have defied clinical repair strategies. My work spans the design and preclinical evaluation of implants intended to drive the cell community of injured muscle toward a regenerative state, as well as the development of an understanding of the molecular responses of this cell community to biomaterial interventions. I demonstrate a new class of biomaterial by leveraging the productive capacity of sacrificial hollow fiber membrane cell culture; I show specifically that unique threads of whole extracellular matrix can be isolated by solvent degradation …

Bioproduction Of Adipic Acid Using Engineered Pseudomonas Putida Kt2440 From Lignin-Derived Aromatics, Howard Willett

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Current industrial synthesis of adipic acid is nonrenewable and depends on a carcinogenic starting material, benzene. Biocatalysis with an engineered microorganism could turn a renewable feedstock into a value-added chemical such as adipic acid. Here we engineered P. putida KT2440 to transform lignin-derived aromatics, coumarate and ferulate, into adipic acid. Lignin is a recalcitrant plant biopolymer burned for thermal energy. Conversion of lignin into a value-added chemical will improve the efficiency of lignocellulose processing plants. The best performing engineered KT2440 strain produces 2.52 mM adipate at a 9.5% (mole/mole) yield. This was achieved by the genetic insertion of non-natural biosynthetic …

Fibrinogen, Factor Xiii And Fibronectin: A Biophysical And Kinetic Characterization Of Their Interactions, Frank Fabian

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

The development of recombinant-based liquid fibrin tissue sealants having enhanced hemostatic and wound healing properties will involve understanding as yet not well characterized interactions between fibrinogen, fibrin (Fbn) factor XIII, thrombin and fibronectin. We study these phenomena in the context of comparing plasma derived fibrinogen to recombinant fibrinogen (rFI) produced in the milk of transgenic cows. An abundance of purified γγ and γγ’ FI subspecies enables detailed study of γγ or γγ’ biomonomer and their respective Fbn biopolymer formation as having different substrate behaviors of activated plasma derived factor XIII (pFXIIIa₂b₂). High pressure size exclusion (HPSEC) …

Maximizing And Modeling Malonyl-Coa Production In Escherichia Coli, Tatiana Thompson Silveira Mello

LSU Master's Theses

In E. coli, fatty acid synthesis is catalyzed by the enzyme acetyl-CoA carboxylase (ACC), which converts acetyl-CoA into malonyl-CoA. Malonyl-CoA is a major building block for numerous of bioproducts. Multiple parameters regulate the homeostatic cellular concentration of malonyl-CoA, keeping it at a very low level. Understanding how these parameters affect the bacterial production of malonyl-CoA is fundamental to maximizing it and its bioproducts. To this end, competing pathways consuming malonyl-CoA can be eliminated, and optimal nutritional and environmental conditions can be provided to the fermentation broth. Most previous studies utilized genetic modifications, expensive consumables, and high-cost quantification methods, making …

The Effect Of Calcination Rate On The Structure Of Mesoporous Bioactive Glasses, Saidur Rahman, Andrew Mendonca, Adel Alhalawani, Deanna Polintan, Owen M. Clarkin, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Mesoporous bioactive glasses (MBGs) are designed to have high specific surface area. They are formulated by a sol–gel process to formulate the glass followed by calcination. This study evaluates how calcination heating rate influences the porous architecture, and thereby the specific surface area, of MBGs. MBGs of molar ratio 80:15:5 for SiO₂ :CaO:P₂ O 5 were calcined using both low (1 °C/min) and high (20 °C/min) heating rates, termed as L-MBG and H-MBG, respectively. The results obtained from small-angle X-ray diffraction (SAXRD) confirm that the MBGs possess 2D hexagonal (P6mm) spacing groups and wide-angle XRD confirms the amorphicity …

Raman Spectroscopy As A Predictive Tool For Monitoring Osteoporosis Therapy In A Rat Model Of Postmenopausal Osteoporosis, J. Renwick Beattie, Antonia Sophocleous, M. Clare Caraher, Olive O'Driscoll, Niamh M. Cummins, Steven E.J. Bell, Mark R. Towler, Alireza Rahimnejad Yazdi, Stuart H. Ralston, Aymen I. Idris

Chemical and Biochemical Engineering Faculty Research & Creative Works

Pharmacological therapy of osteoporosis reduces bone loss and risk of fracture in patients. Modulation of bone mineral density cannot explain all effects. Other aspects of bone quality affecting fragility and ways to monitor them need to be better understood. Keratinous tissue acts as surrogate marker for bone protein deterioration caused by oestrogen deficiency in rats. Ovariectomised rats were treated with alendronate (ALN), parathyroid hormone (PTH) or estrogen (E2). MicroCT assessed macro structural changes. Raman spectroscopy assessed biochemical changes. Micro CT confirmed that all treatments prevented ovariectomy-induced macro structural bone loss in rats. PTH induced macro structural changes unrelated to ovariectomy. …

The Endocytotic Fate Of A Mesoporous Silica Nanoparticle Supported Lipid Bylayer Crispr Delivery Vehicle, Angelea Maestas-Olguin

2019 Award Winners

No abstract provided.

Well-Ordered Mesoporous Silica And Bioactive Glasses: Promise For Improved Hemostasis, Sara Pourshahrestani, Nahrizul Adib Kadri, Ehsan Zeimaran, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Immediate control of uncontrolled bleeding and infection are essential for saving lives in both combat and civilian arenas. Inorganic well-ordered mesoporous silica and bioactive glasses have recently shown great promise for accelerating hemostasis and infection control. However, to date, there has been no comprehensive report assessing their specific mechanism of action in accelerating the hemostasis process and exerting an antibacterial effect. After providing a brief overview of the hemostasis process, this review presents a critical overview of the recently developed inorganic mesoporous silica and bioactive glass-based materials proposed for hemostatic clinical applications and specifically investigates their unique characteristics that render …

Modification Of Lipid Microenvironments On Solid Support Structures For Use In Transmembrane Protein Assays, William J. Houlihan

Dissertations and Theses

Gamma-Secretase (γ-secretase) is a transmembrane protease of increasing interest, which has been shown to have significant connections to both cancer and Alzheimer’s disease. γ-secretase cleaves both Notch-1, a transmembrane signaling protein, and Amyloid precursor protein (APP), a transmembrane protein whose cleavage may result in the formation of β-amyloid plaques in the brain. Notch-1 and APP are widely studied proteins that have substantial impacts on the development and proliferation of cancer and Alzheimer’s disease, respectively. Notch-1 partakes in the signaling of apoptosis in damaged and mutated cells, thus its cleavage by γ-secretase within the plasma membrane has ramifications on cell growth …

Effects Of Micro-Features On Cell Detachment From Poly(N-Isopropylacrylamide) Coated Polydimethylsiloxane Membranes, Luke Webel

Williams Honors College, Honors Research Projects

The tested hypothesis was that features on polydimethylsiloxane (PDMS) surfaces coated with a poly(N-isopropylacrylamide)/aminopropyltriethoxysilane or pNIPAAM/APTES thin film would accelerate cell detachment than the film coated on a unfeatured surface. This project tested samples with features generated by molds, wrinkling, and sandpaper roughened substrates. Surface feature generation methods were limited to mechanical means, and characterized by microscopy and strain rates. 50/50 mixtures of 1.5 wt.% pNIPAAM/ APTES were used to coat thin films (30-40 nm) on PDMS membranes by spin-coating, and the coated membranes were thermally annealed to chemically graft pNIPAAm/APTES on the membrane and their thermo-responsive property was assessed …

Fabrication And Characterization Of Nanofiber Nylon-6-Mwcnt As An Electrochemical Sensor For Sodium Ions Concentration Detection In Sweat, Kelsey Mills

Williams Honors College, Honors Research Projects

Fabrication and characterization nylon-6-MWCNT nanofiber as an electrochemical sensor to detect sodium ion concentrations specifically in sweat. Using contact angle to determine surface morphology and chronoamperometry testing to identify ideal sensor conditions, tests optimized parameters like weight percent of nylon or other polymers, carbon nanotube (CNT) isomer, and solution concentration to determine reproducibility of functional sensors. Utilizing the electric qualities of carbon nanotubes partnered with the sodium ion selectivity of calixarene treatment and polymers unique properties like flexibility and scalability create open an arena for optimizing sodium ion sensors for further development for functional prototypes. Morphology tests showed that the …

Intensification Of Gas Absorption In A Downward Flow Microbubble Bioreactor, Manizheh Ansari

Dissertations and Theses

Bioreactors are of interest for value-upgrading of stranded or waste industrial gases, such as CO, CH₄, or syngas. Process economics requires reduction of reactor cost and size while maintaining high production rate via rapid delivery of gas feedstock to the liquid phase which in turn requires a high volumetric mass transfer rate (). One strategy to achieve this goal is to increase interfacial area density, a, to >3000 m² m^-3, while minimizing use of energy. Here we show a novel reactor column design that uses a micro-jet array to break feedstock at ambient pressure …

Cell Surface Coatings For Mammalian Cell-Based Therapeutic Delivery, Pei-Jung Wu

Theses and Dissertations--Chemical and Materials Engineering

The cell plasma membrane is an interactive interface playing an important role in regulating cell-to-cell, cell-to-tissue contact, and cell-to-environment responses. This environment-responsive phospholipid layer consisting of multiple dynamically balanced macromolecules, such as membrane proteins, carbohydrate and lipids, is regarded as a promising platform for various surface engineering strategies. Through different chemical modification routes, we are able to incorporate various artificial materials into the cell surface for biomedical applications in small molecule and cellular therapeutics.

In this dissertation, we establish two different cell coating techniques for applications of cell-mediated drug delivery and the localization of cell-based therapies to specific tissues. The …

Exploring The Role And Impact Of Microscale Phenomena On Electrode, Microdevice, And Cellular Function, Sanaz Habibi

Dissertations, Master's Theses and Master's Reports

Microfluidic technologies enable the development of portable devices to perform multiple high-resolution unit operations with small sample and reagent volumes, low fabrication cost, facile operation, and quick response times. Microfluidic platforms are expected to effectively interpret both wanted and unwanted phenomena; however, a comprehensive evaluation of the unwanted phenomena has not been appropriately investigated in the literature. This work explored an attenuative evaluation of unwanted phenomena, also called here as secondary phenomena, in a unique approach.

Upon electric field utilization within microfluidic devices, electrode miniaturization improves device sensitivity. However, electrodes in contact with medium solution can yield byproducts that can …

Direct Quantification Of Deubiquitinating Enzyme Activity In Single Intact Cells, Nora Safabakhsh

LSU Doctoral Dissertations

Challenges in drug efficacy occur during the treatment of most types of cancer due to the heterogeneity of the tumor microenvironment. This has led to the development of personalized medicine. Due to the clinical success of the proteasome inhibitors Bortezomib and Carfilzomib in treatment of multiple myeloma, interest has shifted towards molecularly-targeted chemotherapeutics for ubiquitin-proteasome system (UPS). Deubiquitinating enzymes (DUBs) are an essential part of this pathway which have been found to promote Bortezomib resistance in multiple myeloma patients. Unfortunately, there is a lack of specific, high throughput biochemical assays to characterize DUB activity in patient samples before and after …

Uncoupling Fermentative Synthesis Of Molecular Hydrogen From Biomass Formation In Thermotoga Maritima, Raghuveer Singh, Derrick White, Yaşar Demirel, Robert Kelley, Kenneth Noll, Paul H. Blum

Department of Chemical and Biomolecular Engineering: Faculty Publications

When carbohydrates are fermented by the hyperthermophilic anaerobe Thermotoga maritima, molecular hydrogen (H₂) is formed in strict proportion to substrate availability. Excretion of the organic acids acetate and lactate provide an additional sink for removal of excess reductant. However, mechanisms controlling energy management of these metabolic pathways are largely unexplored. To investigate this topic, transient gene inactivation was used to block lactate production as a strategy to produce spontaneous mutant cell lines that overproduced H₂ through mutation of unpredicted genetic targets. Single-crossover homologous chromosomal recombination was used to disrupt lactate dehydrogenase (encoded by ldh) with …

Incorporating Germanium Oxide Into The Glass Phase Of Novel Zinc/Magnesium-Based Gpcs Designed For Bone Void Filling: Evaluating Their Physical And Mechanical Properties, Basel A. Khader, Omar Rodriguez, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

The structural role of Germanium (Ge), when substituting for Zinc (Zn) up to 8 mol % in the 0.48SiO₂-0.12CaO-0.36ZnO-0.04MgO glass series, was investigated with respect to both the glass chemistry and also the properties of glass polyalkenoate cements (GPCs) manufactured from them. The Network connectivity (NC) of the glass was calculated to increase from 1.83 to 2.42 with the addition of GeO₂ (0-8 mol %). Differential thermal analysis (DTA) results confirmed an increase in the glass transition temperature (T_g) of the glass series with GeO₂ content. X-ray photoelectron spectroscopy (XPS) showed an increase in …

Distribution And Localization Of Novel Iodine Nanoparticles In The Human Glioma 1242 Growing In The Brains Of Mice, Benjamin Billings

Honors Scholar Theses

Observing and designing the in vivo distribution and localization of therapeutic nanoparticles is an essential aspect of developing and understanding novel nanoparticle- based medical treatments. This study investigates novel PEGylated Iodine-based nanoparticles (INPs), an alternate composition to the more widely researched gold nanoparticles (AuNPs), which may help avoid adverse effects associated with AuNPs, such as potential toxicity and skin discoloration, when used in similar applications. Determining the localization of the novel INPs within murine brains containing human glioma U-1242MG cells is critical in assisting the development of radiation dose enhancement therapy for this aggressive cancer. Radiation dose enhancement utilizes the …

Preparation Of Supramolecular Amphiphilic Cyclodextrin Bilayer Vesicles For Pharmaceutical Applications, Kate E. Frischkorn

Master's Theses

Recent pharmaceutical developments have investigated using supramolecular nanoparticles in order to increase the bioavailability and solubility of drugs delivered in various methods. Modification of the carbohydrate cyclodextrin increases the ability to encapsulate hydrophobic pharmaceutical molecules by forming a carrier with a hydrophobic core and hydrophilic exterior. Guest molecules are commonly added to these inclusion complexes in order to add stability and further increase targeting abilities of the carriers. One such guest molecule is adamantine combined with a poly(ethylene glycol) chain. Vesicles are formed by hydrating a thin film of amphiphilic cyclodextrin and guest molecules in buffer solution that mimics physiological …

Modeling Pharmaceutical Inhibition Of Glucose-Stimulated Renin-Angiotensin System In Kidneys, Ashlee N. Ford Versypt, Minu R. Pilvankar, Hui Ling Yong

Biology and Medicine Through Mathematics Conference

No abstract provided.

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …