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June 2016 - December 2019
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Publications (111)
Biomanufacturing enables novel sources of compounds with constant demand, such as food coloring and preservatives, as well as new compounds with peak demand, such as diagnostics and vaccines. The COVID-19 pandemic has highlighted the need for alternative sources of research materials, thrusting research on diversification of biomanufacturing platfo...
Food production and pharmaceutical synthesis are posited as essential biotechnologies for facilitating human exploration beyond Earth. These technologies not only offer critical green space and food agency to astronauts but also promise to minimize mass and volume requirements through scalable, modular agriculture within closed-loop systems, offeri...
Potyvirus lactucae, lettuce mosaic virus (LMV), is a devastating pathogen that impacts commercial lettuce production. The complete genome sequence of an LMV isolate from a romaine lettuce plant (LMV-R) collected in 1994 in the Salinas Valley of California was determined by RNA-seq and Sanger sequencing, followed by 5′ rapid amplification of cDNA en...
Food production and pharmaceutical synthesis are posited as essential biotechnologies for facilitating human exploration beyond Earth. These technologies not only offer critical green space and food agency to astronauts but also promise to minimize mass and volume requirements through scalable, modular agriculture within closed-loop systems, offeri...
Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) hold great potential in regenerative medicine. These cells can be expanded indefinitely in theory and are able to differentiate into different types of cells for cell therapies, drug screening and basic biology studies. The reliable and effective propagation of hESCs and...
Efficient resource utilization in small-scale farms is crucial to achieving farm sustainability through endogenous mechanisms. However, the precise mechanisms to integrate farm resources to achieve farm sustainability are not very clear yet. By capturing the interaction among farm resources as a network phenomenon, we aimed to identify the discrete...
In Rwanda, cattle and milk hold a cultural and historical significance, providing an opportunity for pro-dairy governmental policies aimed to alleviate food insecurity, malnutrition, and improve livelihoods. The government of Rwanda has identified strategies to grow the dairy sector through strategic investment to achieve these goals. It is estimat...
Increases in global meat demands cannot be sustainably met with current methods of livestock farming, which has a substantial impact on greenhouse gas emissions, land use, water consumption, and farm animal welfare. Cultivated meat is a rapidly advancing technology that produces meat products by proliferating and differentiating animal stem cells i...
Advancements in understanding and engineering of virus-based nanomaterials (VBNs) for biomedical applications motivate a need to explore the interfaces between VBNs and other biomedically-relevant chemistries and materials. While several strategies have been used to investigate some of these interfaces with promising initial results, including VBN-...
The study was conducted in South 24 Parganas district of West Bengal with the objective of identifying the existing farming systems, its sustainability and income generation capability. The study reveals that the existing farming systems hardly generates income of 100/day and employ only 11.89 percent of workforce for an average family size of five...
Microgravity-induced bone loss is a main obstacle for long term space missions as it is difficult to maintain bone mass when loading stimuli is reduced. With a typical bone mineral density loss of 1.5% per month of microgravity exposure, the chances for osteoporosis and fractures may endanger astronauts’ health. Parathyroid Hormone or PTH (1–34) is...
Making statistical inference on quantities defining various characteristics of a temporally measured biochemical process and analyzing its variability across different experimental conditions is a core challenge in various branches of science. This problem is particularly difficult when the amount of data that can be collected is limited in terms o...
Microgravity-induced bone loss is a main obstacle for long term space missions as it is difficult to maintain bone mass when loading stimuli is reduced. With a typical bone mineral density loss of 1.5% per month of microgravity exposure, the chances for osteoporosis and fractures may endanger astronauts' health. Parathyroid Hormone or PTH (1-34) is...
SARS‐CoV‐2 Spike is a key protein that mediates viral entry into cells and elicits antibody responses. Its importance in infection, diagnostics, and vaccinations has created a large demand for purified Spike for clinical and research applications. Spike is difficult to express, prompting modifications to the protein and expression platforms to impr...
Space bioprocess engineering (SBE) is an emerging multi-disciplinary field to design, realize, and manage biologically-driven technologies specifically with the goal of supporting life on long term space missions. SBE considers synthetic biology and bioprocess engineering under the extreme constraints of the conditions of space. A coherent strategy...
The virus-based immunosorbent nanoparticle is a nascent technology being developed to serve as a simple and efficacious agent in biosensing and therapeutic antibody purification. There has been particular emphasis on the use of plant virions as immunosorbent nanoparticle chassis for their diverse morphologies and accessible, high yield manufacturin...
Technoeconomic modeling and simulation is a critical step in defining a manufacturing process for evaluation of commercial viability and to focus experimental process research and development efforts. Technoeconomic analysis (TEA) is increasingly demanded alongside scientific innovation by both public and private funding agencies to maximize effici...
Reinvigorated public interest in human space exploration has led to the need to address the science and engineering challenges described by NASA's Space Technology Grand Challenges (STGCs) for expanding the human presence in space. Here we define Space Bioprocess Engineering (SBE) as a multi-disciplinary approach to design, realize, and manage a bi...
Reinvigorated public interest in human space exploration has led to the need to address the science and engineering challenges described by NASA's Space Technology Grand Challenges (STGCs) for expanding the human presence in space. Here we define Space Bioprocess Engineering (SBE) as a multi-disciplinary approach to design, realize, and manage a bi...
SARS-CoV-2 Spike is a key protein that mediates viral entry into cells and elicits antibody responses. Its importance in infection, diagnostics, and vaccinations has created a large demand for purified Spike for clinical and research applications. Spike is difficult to express, prompting modifications to the protein and expression platforms to impr...
Highly detailed steered Molecular Dynamics simulations are performed on differently glycosylated receptor binding domains of the SARS-CoV-2 spike protein. The binding strength and the binding range increases with glycosylation. The interaction energy rises very quickly with pulling the proteins apart and only slowly drops at larger distances. We se...
Advancements in understanding and engineering of virus-based nanomaterials (VBNs) for biomedical applications motivate a need to explore the interfaces between VBNs and other biomedically-relevant chemistries and materials. While several strategies have been used to investigate some of these interfaces with promising initial results, including VBN-...
The virus-based immunosorbent nanoparticle is a nascent technology being developed to serve as a simple and efficacious agent in biosensing and therapeutic antibody purification. There has been particular emphasis on the use of plant virions as immunosorbent nanoparticle chassis for their diverse morphologies and accessible, high yield manufacturin...
There are medical treatment vulnerabilities in longer-duration space missions present in the current International Space Station crew health care system with risks, arising from spaceflight-accelerated pharmaceutical degradation and resupply lag times. Bioregenerative life support systems may be a way to close this risk gap by leveraging in situ re...
Transgenic rice cells (Oryza sativa) producing recombinant butyrylcholinesterase (BChE) as a prophylactic/therapeutic against organophosphate nerve agent poisoning, cocaine toxicity, and neurodegenerative diseases like Alzheimer's were immobilized in a polyethylene glycol-based hydrogel. The cells were sustained for 14 days in the semi-solid matrix...
This data article is related to the research article, “M.J. McNulty, K. Kelada, D. Paul, S. Nandi, and K.A. McDonald, Introducing uncertainty quantification to techno-economic models of manufacturing field-grown plant-made products, Food Bioprod. Process. 128 (2021) 153-165.” The raw and analyzed data presented are related to generation, analysis,...
Infectious diseases, also known as transmissible or communicable diseases, are caused by pathogens or parasites that spread in communities by direct contact with infected individuals or contaminated materials, through droplets and aerosols, or via vectors such as insects. Such diseases cause ~17% of all human deaths and their management and control...
The fight against infectious diseases often focuses on epidemics and pandemics, which demand urgent resources and command attention from the health authorities and media. However, the vast majority of deaths caused by infectious diseases occur in endemic zones, particularly in developing countries, placing a disproportionate burden on underfunded h...
A crewed mission to and from Mars may include an exciting array of enabling biotechnologies that leverage inherent mass, power, and volume advantages over traditional abiotic approaches. In this perspective, we articulate the scientific and engineering goals and constraints, along with example systems, that guide the design of a surface biomanufact...
Highly detailed steered Molecular Dynamics simulations are performed on differently glycosylated receptor binding domains of the SARS-CoV-2 spike protein. The binding strength and the binding range increases with glycosylation. The interaction energy rises very quickly with pulling the proteins apart and only slowly drops at larger distances. We se...
There is a growing demand for large-market natural and biotechnological products driven by shifting consumer preferences in food and calls for decentralized vaccine and medication production capabilities. The current paradigm of bioreactor-based biomanufacturing faces difficulties of scalability and a high entry barrier of capital intensity and wor...
There are medical treatment vulnerabilities in longer-duration space missions present in the current International Space Station crew health care system with risks, arising from spaceflight-accelerated pharmaceutical degradation and resupply lag times. Bioregenerative life support systems may be a way to close this risk gap by leveraging in situ re...
There are currently worldwide efforts to reduce sugar intake due to the various adverse health effects linked with the overconsumption of sugars. Artificial sweeteners have been used as an alternative to nutritive sugars in numerous applications; however, their long-term effects on human health remain controversial. This led to a shift in consumer...
We propose a method for analyzing the variability in smooth, possibly nonlinear, functionals associated with a set of product production trajectories measured under different experimental conditions. The key challenge is to make meaningful inference on these parameters across different experimental conditions when only a limited number of measureme...
Space missions have always assumed that the risk of spacecraft malfunction far outweighs the risk of human system failure. This assumption breaks down for longer duration exploration missions and exposes vulnerabilities in space medical systems. Space agencies can no longer reduce the majority of the human health and performance risks through crew...
There is a growing demand for large market natural and biotechnological products, for example, consumer preferences drive plant-based meat alternatives, health risks of sugar overconsumption continue to motivate alternative sweeteners, and the COVID-19 pandemic has reinvigorated interest in countries developing in-house vaccine and medication produ...
Transgenic rice cells ( Oryza sativa ) producing recombinant butyrylcholinesterase (BChE) as a prophylactic/therapeutic against organophosphate nerve agent poisoning, cocaine toxicity, and neurodegenerative diseases like Alzheimer′s were immobilized in a polyethylene glycol-based hydrogel. The cells were sustained for 14 days in the semi-solid matr...
Alpha-1 antitrypsin deficiency (A1ATD) is an autosomal recessive disease characterized by low plasma levels of A1AT, a serine protease inhibitor representing the most abundant circulating antiprotease normally present at plasma levels of 1–2 g/L. The dominant clinical manifestations include predispositions to early onset emphysema due to protease/a...
A crewed mission to and from Mars may include an exciting array of enabling biotechnologies that leverage inherent mass, power, and volume advantages over traditional abiotic approaches. In this perspective, we articulate the scientific and engineering goals and constraints, along with example systems, that guide the design of a surface biomanufact...
Producing recombinant proteins in transgenic plant cell suspension cultures in bioreactors provides controllability, reproducibility, scalability, and low‐cost production, although low yields remain the major challenge. The studies on scaling‐up to pilot‐scale bioreactors, especially in conventional stainless‐steel stirred tank bioreactors (STB), t...
Shrinking farm size and fragile farm resources pose a significant challenge to the sustainability of small-scale farms. Efficient resource utilization in small-scale farms is crucial to achieving farm sustainability through endogenous mechanisms. However, the precise mechanisms to integrate physical resources to achieve farm sustainability are not...
There are currently worldwide efforts to reduce sugar intake due to the various adverse health effects linked with the overconsumption of sugars. Artificial sweeteners have been used as an alternative to nutritive sugars in numerous applications; however, their long-term effects on human health remain controversial. This led to a shift in consumer...
Transgenic plant cell suspension culture is a promising platform for recombinant protein production. Rice cell suspension culture is one of the systems that has been developed due to its unique metabolically-regulated promoter, rice alpha-amylase 3D (RAmy3D), that is up-regulated in sugar-deprived medium. Using the RAmy3D promoter system in transge...
Several epidemic and pandemic diseases have emerged over the last 20 years with increasing reach and severity. The current COVID-19 pandemic has affected most of the world’s population, causing millions of infections, hundreds of thousands of deaths, and economic disruption on a vast scale. The increasing number of casualties underlines an urgent n...
The cover image is based on the Original Article Techno‐economic analysis of semicontinuous bioreactor production of biopharmaceuticals in transgenic rice cell suspension cultures by Matthew McNulty et al., https://doi.org/10.1002/bit.27475.
The production and N-glycosylation of recombinant human butyrylcholinesterase (BChE), a model highly glycosylated therapeutic protein, in a transgenic rice cell suspension culture treated with kifunensine, a strong α-mannosidase I inhibitor, was studied in a 5 L bioreactor. A media exchange was performed at day 7 of cultivation by removing spent su...
Space missions have always assumed that the risk of spacecraft malfunction far outweighs the risk of human system failure. This assumption breaks down for longer duration exploration missions and exposes vulnerabilities in space medical system. Space agencies can no longer buy down the majority of human system risk through the crew member selection...
The production and N-glycosylation of recombinant human butyrylcholinesterase (BChE), a model highly glycosylated therapeutic protein, in a transgenic rice cell suspension culture treated with kifunensine, a strong α-mannosidase I inhibitor, was studied in a 5 L bioreactor. A media exchange was performed at day 7 of cultivation by removing spent su...
We develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. These models are tested in their interaction with a fragment of the receptor-binding domain (RBD) of the Spike Protein S of the SARS-CoV-2 virus, via atomistic molecular dynamics simulations. We see that some ACE2 gl...
Metabolically regulated transgenic rice cell suspension culture has been developed aiming to be an efficient and cost-effective platform for production of rice-recombinant butyrylcholinesterase (rrBChE) that could be used as a bioscavenger enzyme against organophosphate nerve agents. In two-stage batch cultures, switching between growth and inducti...
Biopharmaceutical protein production using transgenic plant cell bioreactor processes offers advantages over microbial and mammalian cell culture platforms in its ability to produce complex biologics with simple chemically defined media and reduced biosafety concerns. A disadvantage of plant cells from a traditional batch bioprocessing perspective...
We develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. These models are tested in their interaction with fragments of the binding domain of the Spike Protein S1 of the SARS-CoV-2 virus. We see that some ACE2 glycans interact with S1 and glycans are influencing the confor...
Continuous reports of foodborne illnesses worldwide and the prevalence of antibiotic‐resistant bacteria mandate novel interventions to assure the safety of our food. Treatment of a variety of foods with bacteriophage‐derived lysins and bacteriocin‐class antimicrobial proteins has been shown to protect against high‐risk pathogens at multiple interve...
Protein N-glycosylation is an important post-translational modification and has influences on a variety of biological processes at the cellular and molecular level, making glycosylation a major study aspect for glycoprotein-based therapeutics. To achieve a comprehensive understanding on how N-glycosylation impacts protein properties, an Fc-fusion a...
N-glycosylation has been shown to affect the pharmacokinetic properties of several classes of biologics, including monoclonal antibodies, blood factors, and lysosomal enzymes. In the last two decades, N-glycan engineering has been employed to achieve a N-glycosylation profile that is either more consistent or aligned with a specific improved activi...
N-glycosylation has been shown to affect the pharmacokinetic properties of several classes of biologics including monoclonal antibodies, blood factors, and lysosomal enzymes. In the last two decades, N-glycan engineering has been employed to achieve a N-glycosylation profile that is either more consistent or aligned with a specific improved activit...
Butyrylcholinesterase (BChE) is a glycosylated serine hydrolase found in human serum that has been shown to protect against various cholinesterase-inhibiting organophosphate nerve agents. The supply of plasma-derived butyrylcholinesterase (hBChE) is constrained by the availability of human blood and a complex purification process and its high cost....
Griffithsin is a marine algal lectin that exhibits broad-spectrum antiviral activity by binding oligomannose glycans on viral envelope glycoproteins, including those found in HIV-1, HSV-2, SARS, HCV and other enveloped viruses. An efficient, scalable and cost-effective manufacturing process for Griffithsin is essential for the adoption of this drug...
Transient recombinant protein production is a promising alternative to stable transgenic systems, particularly for emergency situations in which rapid production of novel therapeutics is needed. In plants, Agrobacterium tumefaciens can be used as a gene delivery vector for transient expression. A potential barrier for plant-based production of huma...
Kifunensine, a potent and selective inhibitor of class I α-mannosidases, prevents α-mannosidases I from trimming mannose residues on glycoproteins, thus resulting in oligomannose-type glycans. We report for the first time that through one-time vacuum infiltration of kifunensine in plant tissue, N-linked glycosylation of a recombinant protein transi...
Recombinant butyrylcholinesterase produced in a metabolically-regulated transgenic rice cell culture (rrBChE) was purified to produce a highly pure (95%), active form of enzyme. The developed downstream process uses common manufacturing-friendly operations including tangential flow filtration, anion-exchange chromatography, and affinity chromatogra...
Anthrax toxin receptor-mediated drug development for blocking anthrax toxin action has received much attention in recent decades. In this study, we produced a secreted anthrax decoy fusion protein comprised of a portion of the human capillary morphogenesis gene-2 (CMG2) protein fused via a linker to the fragment crystallizable (Fc) domain of human...
The need for sustainable agricultural advancements remain at the forefront of global development practices, with smallholder farms emerging as an essential factor in creating long-lasting improvements in food security, enhanced nutrition, and economic development. Sustainable intensification and diversification in small farms can achieve these outc...
Plant-based biomanufacturing of therapeutic proteins is a relatively new platform with a small number of commercial scale facilities, but offers advantages of linear scalability, reduced upstream complexity, reduced time to market, and potentially lower capital and operating costs. In this study we present a detailed process simulation model for a...
To optimize the expression, extraction and purification of plant-derived tetrameric recombinant human butyrylcholinesterase (prBChE), we describe the development and use of plant viral amplicon-based gene expression system; Tobacco Mosaic Virus (TMV) RNA-based overexpression vector (TRBO) to express enzymatically active FLAG-tagged plant made recom...
Increasing economic and educational exposure, and promotion of global health and wellness can be achieved through the power of sharing knowledge, technology, and resources. ICT can play a key role in disseminating such knowledge across the world. But a digital divide exists between urban and rural/remote areas, which results in economic and social...
An active and tetrameric form of recombinant butyrylcholinesterase (BChE), a large and complex human enzyme, was produced via semicontinuous operation in a transgenic rice cell suspension culture. After transformation of rice callus and screening of transformants, the cultures were scaled up from culture flask to a lab scale bioreactor. The bioreac...
The impact of non-farm activity on rural income inequality in the South 24 Parganas district of West Bengal has been studied. The non-agricultural activities play a key role in shoring up income and employment opportunities for the rural work force in this district. The average annual income of nonfarm families ( 108662) is almost double to that of...
The goal to increase global economic citizenship and educational exposure, and to promote global health and wellness, can be achieved through the power of sharing knowledge, technology, and resources. Computing and Information and Communication Technology (ICT) services can play an important role in disseminating such knowledge around the world. Bu...
Milk spoilage and low quality milk are of special concern to developing countries such as Rwanda. Our objective was to measure bacterial loads in milk via total bacterial count (TBC) in three major segments of the dairy value chain from farm to consumer, including milk transporters, milk collection centers, and milk kiosks. In all cases, the increa...
Production of heterologous proteins for human therapeutics in plant-based platform is becoming commercially acceptable. Plant expression systems have several advantages, such as lower capital investment, low maintenance cost, absence of human pathogens, and complex posttranslational glycosylation capabilities. Recently, significant advances have be...
Food safety and milk quality begin on the farm. Dairy Dynamic Management (DDM) is a way to identify existing and future problems before they occur. We do this through team-building, listening to one another, problem solving together, and implementing the DDM process. In this project, we focused on mastitis control as the economic and animal well-be...
The study was carried out to find the profitability and resource use efficiency of two fish production system i.e. wastewater and freshwater in West Bengal, India. The study revealed that though the productivity of freshwater fish production system was higher by 74.5 kg/acre over the other system but the freshwater fish production farmers realized...
Abstracts:
* Final abstract 2014 AICHE annula meeting.docx (16.5KB) - Uploading Abstracts
This book describes the most recent research involving the generation of vaccines and other therapeutic proteins for combating infectious diseases which predominate in developing countries.
Human butyrylcholinesterase (hBChE EC 3.1.1.8) is a 574 amino acid cholinesterase-hydrolyzing enzyme. Organophosphates (OP) are highly toxic inhibitors of the acetylcholine-hydrolyzing enzymes like hBChE. The resulting accumulation of acetylcholine can lead to respiratory collapse and death. Current therapies are based on elevating the serum levels...
The goal to increase global economic citizenship and educational exposure, and to promote global health and wellness, can be achieved through the power of sharing knowledge, technology, and resources. Computing and Information and Communication Technology (ICT) services can play an important role in disseminating such knowledge around the world. Bu...
Knowledge of the human genome sequence combined with the ability to design evidence based therapeutic nutrition creates an unprecedented opportunity to promote global health and wellness for vulnerable populations around the world. By matching diet according to naturally occurring human genetic variation, researchers, educators, and policy makers s...
Transferrin is an essential ingredient used in cell culture media due to its crucial role in regulating cellular iron uptake, transport, and utilization. It is also a promising drug carrier used to increase a drug's therapeutic index via the unique transferrin receptor-mediated endocytosis pathway. Due to the high risk of contamination with blood-b...
Human alpha-1-antitrypsin (AAT), the most abundant protease inhibitor found in the blood, was expressed in rice embryonic tissue suspension cell culture. This was accomplished by cloning the codon-optimized AAT gene into a vector containing the rice RAmy3D promoter and its signal sequence. The synthetic gene incorporates codons synonymous with thos...
In this paper, we show that recombinant human lactoferrin (rhLF) has been stably expressed at 0.5% brown rice flour weight for nine generations. Process development indicates that rhLF can be efficiently extracted from rice flour in 20 mM phosphate buffer (pH 7.0) containing up to 0.5 M NaCl and at a ratio of 1 kg flour to 10 L buffer. After solid/...
A total of 66 transgenic rice cell lines were produced by simultaneously transforming rice callus with nine different plasmids/genes. PCR analysis indicated that the co-transformation frequency of each gene was about 70%. All the cell lines carried at least three genes and 11 cell lines carried all nine genes. Thirty-two fertile transgenic plants (...
Breast-fed infants are healthier than formula-fed infants, which may in part be due to the lack of components like human lactoferrin (HLF) in infant formula. Thus, fortification of infant formula with bioactive proteins such as recombinant HLF (rHLF) may provide health benefits. A synthetic HLF gene linked to a rice glutelin 1 promoter and signal s...
In the present study, we explored the expression of human lysozyme in maturing rice grains. Particle bombardment-mediated transformation was utilized to deliver the codon-optimized structural gene for human lysozyme to the callus of rice cultivar Taipei 309. Lysozyme expression is controlled by the promoter and signal peptide sequence for rice stor...
The rice globulin (Glb) promoter was analyzed for its ability to control the expression of the human lysozyme gene in transgenic rice grains. The expression of the human lysozyme gene under the control of the Glb promoter reached 23% total soluble protein, with an average of 13%. To search for important elements within the Glb promoter, we analyzed...
Two barley aleurone-specific promoters from genes encoding lipid transfer protein (Ltp1) and chitinase (Chi26), respectively, were transcriptionally fused to a #-glucuronidase gene (GUS). Tissue-specific expression of these GUS chimeric constructs was examined in transgenic rice. Histochemical analysis of individual transformants revealed that G...
The expression of β-glucuronidase (GUS) under the control of a 940 bp rice β-glucanase 9 (Gns9) gene promoter was developmentally regulated and could only be detected in rice calli but not in leaves, roots or seeds. To prevent the accumulation of a selectable marker gene product in transgenic rice seeds, the Gns9 promoter was then fused to the gene...