β-lactoglobulin (BLG) is the major whey protein in ruminants and is found in the milk of a wide range of species. Extensive study of BLG over the years has led to the determination of the structure of the protein at 2.8AA and has revealed its ability to bind a variety of small hydrophobic molecules. However, the physiological function of BLG remains unknown despite its inclusion within the lipocalycin family on the grounds of genetic and tertiary structure comparisons as well as similarities in amino acid sequence. A protein engineering approach was adopted to study the residues involved in subunit interactions and ligand binding as well as the importance of Cys119 and 121 in determining the stability of the tertiary structure. The complete coding sequence for ovine BLG was obtained and a convenient site-directed mutagenesis system was set up. An expression system in the yeast Saccharomyces cerevisiae was developed in which ovine BLG was synthesised and secreted into the growth medium. ...
TY - JOUR. T1 - Overcoming low yields of plant-made antibodies by a protein engineering approach. AU - Jansing, Julia. AU - Sack, Markus. AU - Fischer, Rainer PY - 2015. Y1 - 2015. M3 - Article. JO - Biotechnology Journal. JF - Biotechnology Journal. SN - 1860-6768. ER - ...
TY - JOUR. T1 - Rational protein engineering in action. T2 - The first crystal structure of a phenylalanine tRNA synthetase from Staphylococcus haemolyticus. AU - Evdokimov, Artem G.. AU - Mekel, Marlene. AU - Hutchings, Kim. AU - Narasimhan, Lakshmi. AU - Holler, Tod. AU - McGrath, Teresa. AU - Beattie, Bryan. AU - Fauman, Eric. AU - Yan, Chunhong. AU - Heaslet, Holly. AU - Walter, Richard. AU - Finzel, Barry. AU - Ohren, Jeffrey. AU - McConnell, Patrick. AU - Braden, Timothy. AU - Sun, Fang. AU - Spessard, Cindy. AU - Banotai, Craig. AU - Al-Kassim, Loola. AU - Ma, Weijun. AU - Wengender, Paul. AU - Kole, Denis. AU - Garceau, Norman. AU - Toogood, Peter. AU - Liu, Jia. N1 - Funding Information: The authors specifically acknowledge the mass-spectroscopic measurements made by Tracy Stevenson and Eric Lund as well as the biophysical experiments conducted by Ronald Sarver and Kimberly Huchings. Use of the IMCA-CAT beamline 17-ID at the APS was supported by the companies of the Industrial ...
Felton, Calif., USA, Apr. 29, 2021 - /EPR Network/ -. The global Protein Engineering Market research report provides complete insights on industry scope, trends, regional estimates, key application, competitive landscape and financial performance of prominent players. It also offers ready data-driven answers to several industry-level questions. This study enables numerous opportunities for the market players to invest in research and development.. Market Overview:. Global Protein Engineering Market is anticipated to reach USD 3.09 billion by 2025. Protein engineering is a method to design novel proteins or enzymes with the intention to have functional properties. Protein engineering is primarily based on the use of recombinant DNA technology to alter the amino acid sequences in terms of affinity, solubility, activity, resistance, etc.. Key Players:. ...
This protocol describes the computational steps necessary to reproduce the results described in the paper Unified rational protein engineering with sequence-only deep representation learning by Alley et al....
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Ancestral phenylalanine/tyrosine ammonia-lyases have potential for supplementary treatment to Nitisinone of hereditary tyrosinemia. Sci. Rep. , 10, W. Farhat, A. Biundo, A. Stamm, E. Malmström, P.-O. Syrén*. Lactone monomers obtained by enzyme catalysis and their use in reversible thermoresponsive.
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Determination of the histamine content is of paramount importance for the food industry as a parameter of the hygienic quality and freshness of food, as well as to prevent scombroid fish poisoning, an allergy-like food poisoning. At present, more sensitive and user-friendly methods for histamine monitoring are needed to early detect products and raw materials susceptible of becoming hazardous for consumers. BIOIMPROVE aims to develop an improved and highly sensitive portable biosensing device for the quantification of histamine in the lower concentration range (,5 mg/l). To reach this objective, an innovative and powerful semi-rational protein engineering strategy will be used to maximize the sensitivity of the currently available histamine enzyme-based biosensor. Rather than addressing this goal by the generation and screening of large libraries, a careful selection of the most promising mutational hotspots will be performed using the structural available information in tandem with advanced ...
Intrexon’s bioinformatics and computational modeling platform is central to our protein engineering expertise, which focuses on designing enhanced and/or novel protein functionalities, including stability, localization, and catalytic activity.  To modulate these protein properties, we utilize the UltraVector® platform’s modular design method to separate proteins into functional elements.  Our protein engineering utilizes principles of structural biology, computational chemistry, molecular biology and bioinformatics.  Intrexon’s proprietary database of information catalogs comprehensive information about the genetic and protein components based on structure-based sequence alignment, de novo and comparative protein modeling, molecular dynamics simulation and free energy analysis.
/PRNewswire/ -- According to a new market research report Protein Engineering Market by Technology (Rational Protein Design, Irrational Protein Design),...
Protein Engineering LaboratoryWe are interested in protein engineering for the creation and development of new proteins and protein variants. Especially, we are interested in pharmaceutical proteins such as antibody specific for cancer and inflammation
Over the past three decades, a large body of work has been directed at the development of therapeutic cytokines. Despite their central role in immune modulation, only a handful of cytokine therapeutics has achieved regulatory approval. One of the major challenges associated with the therapeutic use of cytokines relates to their short serum half-life and low bioavailability. High doses are required to overcome these problems, which often result in dose-limiting toxicities. Consequently, most cytokines require protein engineering approaches to reduce toxicity and increase half-life. For this purpose, PEGylation, fusion proteins, antibody complexes and mutagenesis have been utilized. Here, we summarize past, recent and emerging strategies in this area.
C1q is the first subcomponent of the classical pathway of the complement system and a major connecting link between innate and acquired immunity. As a versatile charge pattern recognition molecule, C1q is capable of engaging a broad range of ligands via its heterotrimeric globular domain (gC1q) which is composed of the C-terminal regions of its A (ghA), B (ghB) and C (ghC) chains. Recent studies using recombinant forms of ghA, ghB and ghC have suggested that the gC1q domain has a modular organization and each chain can have differential ligand specificity. The crystal structure of the gC1q, molecular modeling and protein engineering studies have combined to illustrate how modular organization, charge distribution and the spatial orientation of the heterotrimeric assembly offer versatility of ligand recognition to C1q. Although the biochemical and structural studies have provided novel insights into the structure-function relationships within the gC1q domain, they have also raised many unexpected issues
AB - Adaptive immune responses characterised by the synthesis of antibodies of the immunoglobulin E (IgE) isotype play an important role in type I hypersensitivity disorders and parasitic infestations, diseases which have an significant socioeconomic impact world-wide. This paper considers potential applications of recent advances in our understanding of the origin of isotype specific immune responses which emerged as a result of cell and protein engineering studies on components of the human IgE/receptor/effector system. Furthermore, the identification of the receptor binding regions in IgE as a result of the development of a stable assay system has important applications for the design of rational therapeutic interventions in allergy and asthma, the treatment of mast cell tumours, and the establishment of procedures for the selective isolation of cells expressing the high-affinity receptor for IgE for functional studies ...
Get this from a library! Therapeutic antibody engineering : current and future advances driving the strongest growth area in the pharmaceutical industry. [W R Strohl; Lila M Strohl] -- The field of antibody engineering has become a vital and integral part of making new, improved next generation therapeutic monoclonal antibodies, of which there are currently more than 300 in ...
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Author: Acevedo Rocha, Carlos Guillermo et al.; Genre: Book Chapter; Published in Print: 2014-08-31; Keywords: deletion mutations - directed evolution - gene variant libraries - insertion mutations - mutagenesis; Title: Iterative Saturation Mutagenesis (ISM): A Powerful Approach to Engineer Proteins by Systematically Simulating Darwinian Evolution
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Antibody Engineering Company f-star Raises EUR 6.0 Million in Series A Financing From Aescap Venture and Atlas Venture VIENNA, Austria, September 10 -- f-star, an antibody engineering company
BACKGROUND: Protein fold recognition usually relies on a statistical model of each fold; each model is constructed from an ensemble of natural sequences belonging to that fold. A complementary strategy may be to employ sequence ensembles produced by computational protein design. Designed sequences can be more diverse than natural sequences, possibly avoiding some limitations of experimental databases. METHODOLOGY/PRINCIPAL FINDINGS: WE EXPLORE THIS STRATEGY FOR FOUR SCOP FAMILIES: Small Kunitz-type inhibitors (SKIs), Interleukin-8 chemokines, PDZ domains, and large Caspase catalytic subunits, represented by 43 structures. An automated procedure is used to redesign the 43 proteins. We use the experimental backbones as fixed templates in the folded state and a molecular mechanics model to compute the interaction energies between sidechain and backbone groups. Calculations are done with the [email protected] volunteer computing platform. A heuristic algorithm is used to scan the sequence and conformational
Le « Computational protein design » ou CPD est la recherche des séquences dacides aminés compatibles avec une structure protéique ciblée. Lobjectif est de concevoir une fonction nouvelle et/ou dajouter un nouveau comportement. Le CPD est en développement dans de notre laboratoire depuis plusieurs années, avec le logiciel Proteus qui a plusieurs succès à son actif.Notre approche utilise un modèle énergétique basé sur la physique et sappuie sur la différence dénergie entre létat plié et létat déplié de la protéine. Au cours de cette thèse, nous avons enrichi Proteus sur plusieurs points, avec notamment lajout dune méthode dexploration Monte Carlo avec échange de répliques ou REMC. Nous avons comparé trois méthodes stochastiques pour lexploration de lespace de la séquence : le REMC, le Monte Carlo simple et une heuristique conçue pour le CPD, le «Multistart Steepest Descent » ou MSD. Ces comparaisons portent sur neuf protéines de trois familles de structures :
Combinatorial protein engineering, taking advantage of large libraries of protein variants and powerful selection technology, is a useful strategy for developing affinity proteins for applications in biotechnology and medicine. In this thesis, two small affinity proteins have been subjected to combinatorial protein engineering to improve or redirect the binding. In two of the projects, a three-helix protein domain based on staphylococcal protein A has been used as scaffold to generate so called Affibody molecules capable of binding to key proteins related to two diseases common among elderly people.. In the first project, Affibody molecules were selected using phage display technology for binding to Ab-peptides, believed to play a crucial role in Alzheimers disease, in that they can oligomerize and contribute to the formation of neural plaques in the brain. The selected Affibody molecules were found to efficiently capture Ab from spiked human plasma when coupled to an affinity resin. The ...
As the population ages, the number of people with neurodegenerative diseases is expected to increase. Antibody therapeutics could be important in the fight against these diseases.
Enzyme engineering is a powerful technology now widely used in laboratories around the world. The goal is to obtain improved proteins that will serve as better biocatalysts, biosensors or as a tool to understand protein evolution, which is at the core of many societal problem, such as antibiotic resistance. Enzyme engineering entails the initial generation of libraries of mutants that will then be screened for improved properties (for example: better selectivity or specificity towards a substrate of interest, improved stability, etc). Obtaining good quality libraries is becoming routine thanks to the availability of molecular biology tools and computational simulations. The bottleneck of the experiment remains at the screening level. The bigger the generated library, the more stringent the requirement for the high-throughput screen ...
Établissement public administratif national placé sous la tutelle du ministre chargé de la recherche. Son siège est situé à Paris.
Ana Dolinar) Dueber, J. E. et al. 2009. Synthetic protein scaffolds provide modular control over metabolic flux. Nature Biotechnology 27: 753-759. The article was written by John E. Dueber and his colleagues and published in Nature Biotechnology in the year 2009. In the research, they used synthetic protein scaffolds to organize metabolic enzymes and thus improve the effectiveness of metabolite synthesis. Following writing will cover the basics of metabolic engineering, protein scaffolds, substrate channeling and mevalonate synthesis as well as experimental results from Duebers paper and a brief comparison of other scaffolding molecules (i.e. DNA, RNA). Introduction Metabolic engineering Metabolic engineering is a term, defined in 1991 by James Edward Bailey as Improvement of cellular activities by manipulation of enzymatic transport and regulatory functions of the cell with the use of recombinant DNA technology (ref=Bailey). These days it is used as a term for describing modifications of ...
Close proximity with a female something that occurs in a majority of species, including humans results in the ejaculates from two or more males overlapping within her reproductive tract.
The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format. By default, clicking on the export buttons will result in a download of the allowed maximum amount of items. To select a subset of the search results, click Selective Export button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export. After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format. ...
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A large-scale study to test the actual stability of computationally designed proteins shows a way to take some of the guesswork out of protein engineering. Previously, scientists tested only a few tens of proteins, due to prohibitive costs of DNA. This new approach, which incorporates advances in DNA synthesis technology, efficiently checks thousands of mini-protein designs. The hope is that in the future a similar approach could test bigger, more complex, designed proteins ...
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PhD Project - Protein engineering enzymes for industry: production and assessment of bile acid products at University of Reading, listed on FindAPhD.com
Protein Engineering: is the process of developing useful or valuable proteins. It is a young discipline, with much research taking place into the understan
G-protein coupled receptors (GPCRs) are integral membrane proteins that share a common seven-transmembrane helix fold topology. They play fundamental roles in most physiological and many pathological processes. Currently, GPCRs are the target of ~30% of all medical drugs. As a result of the major drug discovery activities targeting GPCRs, there is a growing demand for high-resolution structures. Despite enormous efforts, however, progress in the structural characterization of GPCRs is rather slow. Primarily two methods have been developed for structural work on GPCRs: scanning alanine mutagenesis and the fusion protein engineering approach. However, both methods have substantial limitations, emphasizing that the development of new GPCR crystallization tools will be of fundamental importance in moving the field forward. Towards this aim, we developed a novel approach to facilitate the crystallization of GPCRs ...
Transgenic plants expressing combinations of microbial or plant pesticidal proteins represent a promising tool for the efficient, durable control of herbivorous insects. In this review we describe current strategies devised for the heterologous co-expression of pesticidal proteins in planta, some of which have already shown usefulness in plant protection. Emphasis is placed on protein engineering strategies involving the insertion of single DNA constructs within the host plant genome. Multimodal fusion proteins integrating complementary pesticidal functions along a unique polypeptide are first considered, taking into account the structural constraints associated with protein or protein domain grafting to biologically active proteins. Strategies that allow for the co- or post-translational release of two or more pesticidal proteins are then considered, including polyprotein precursors releasing free proteins upon proteolytic cleavage, and multicistronic transcripts for the parallel translation of single
A highly crystallizable T4 lysozyme (T4L) was fused to the N-terminus of the β2 adrenergic receptor (β2AR), a G-protein coupled receptor (GPCR) for catecholamines. We demonstrate that the N-terminal fused T4L is sufficiently rigid relative to the receptor to facilitate crystallogenesis without thermostabilizing mutations or the use of a stabilizing antibody, G protein, or protein fused to the 3rd intracellular loop. This approach adds to the protein engineering strategies that enable crystallographic studies of GPCRs alone or in complex with a signaling partner.
Since your email address was listed on a related web site page or database, I thought you might help. I am seeking an individual within the following conditions: Individual sought to join leading biotech firm researching and developing drugs and diagnostic products using the human gene. Seeking a Research Scientist for the Antibody Engineering group. A Ph.D. in Molecular Biology with 2 years postdoctoral experience is required. Candidate must also have experience with generating and screening phage display libraries and humanization of antibodies. Additional experience with Immunology and/or discovering therapeutic antibodies is highly preferred. This is an opportunity to join an outstanding scientific team on the cutting edge of drug discovery. We offer and outstanding compensation package including relocation. Geographic Location of Position: Mid Atlantic States If you know anyone that might be interested, please forward this to them or contact: Larry Chiaravallo Diedre Moire Corp., Inc. ...
Chemical biology has long sought to build protein switches for use in molecular diagnostics, imaging, and synthetic biology. The overarching challenge for any type of engineered protein switch is the ability to respond in a selective and predictable manner that caters to the specific environments and time scales needed for the application at hand. We previously described a general method to design switchable proteins, called chemical rescue of structure, that builds de novo allosteric control sites directly into a proteins functional domain. This approach entails first carving out a buried cavity in a protein via mutation, such that the proteins structure is disrupted and activity is lost. An exogenous ligand is subsequently added to substitute for the atoms that were removed by mutation, restoring the proteins structure and thus its activity. Here, we begin to ask what principles dictate such switches response to different activating ligands. Using a redesigned β-glycosidase enzyme as ...
Yumab feature in Natures Biopharma Dealmakers describes how the company acts as a driver of the general trend in the immunotherapy space toward the use of fully human mAbs for therapeutic applications. Read more. 1st prize of the Innovationsnetzwerk Niedersachsen 2017 was awarded to Yumab and the TU Braunschweig at the Hannover Messe by the Minister for Science and Culture, Gabriele Heinen-Kljaji, and the Minister for Economics, Employment and Traffic, Olaf Lies. Meet YUMAB CEO Thomas Schirrmann at the J.P. Morgan 35th Annual Healthcare Conference 2017 San Francisco (January 9-12, 2017).. YUMAB cofounder Michael Hust will present YUMAB technologies at Toxins 2017 in Madrid (January 18-21, 2017).. Meet André Frenzel, YUMAB CSO and cofounder, and Michael Hust, YUMAB cofounder, at Antibodies in Drug Discovery in Cambridge, UK (March 6+7, 2017).. Meet YUMAB head of development Dr. Jonas Kügler at the „Antibody Engineering & Therapeutics in San Diego December 11th to 15th at the booth of the ...
The advent of economical gene synthesis is making it easier than ever to engineer completely new proteins. Computational protein design is a promising strategy to take advantage of our new found latitude. Previous computational protein design efforts have led to extraordinarily stable proteins (Tm above 99°C). However, the same algorithms also can lead to unfolded, aggregated, or destabilized proteins. It remains challenging to reliably design properties of interest (structure, stability, catalysis) into synthetic proteins. Furthermore, directed evolution raises the bar for computational design; it is often possible to optimize a protein of interest via screening libraries of random mutants thereof ...
Antibody Engineering & Therapeutics Europe is the industrys European meeting for antibody and protein therapeutic science, technology and networking.
Author(s): Pan, Xingjie | Advisor(s): Kortemme, Tanja | Abstract: Proteins perform most of biological functions. The ultimate approach to understand protein functions is designing novel protein functions from scratch. The ability to design novel functional proteins would also be revolutionary for biology research, medicine and synthetic biology. Proteins function by placing specific chemical groups at precise 3-dimensional (3D) positions and orientations. Therefore, de novo functional protein design relies on precise control of protein 3D structures. In this thesis, I review the recent advances in de novo protein design (chapter 1). Then I describe two of my research projects that aim to extend the ability of computational methods to design precise protein 3D structures. In the first project (chapter 2), I developed a method termed loop-helix-loop unit combinatorial sampling (LUCS) that systematically samples geometries of protein secondary structures. I applied LUCS to designs de novo protein fold
Antibody engineering is the process of developing an antibody with optimal characteristics. Review the details and helpful solutions here.
A principal goal of synthetic biology is the de novo design or redesign of biomolecular components. In addition to revealing fundamentally important information regarding natural biomolecular engineering and biochemistry, functional building blocks will ultimately be provided for applications including the manufacture of valuable products and therapeutics. To fully realize this ambitious goal, the designed components must be biocompatible, working in concert with natural biochemical processes and pathways, while not adversely affecting cellular function. For example, de novo protein design has provided us with a wide repertoire of structures and functions, including those that can be assembled and function in vivo Here we discuss such biocompatible designs, as well as others that have the potential to become biocompatible, including non-protein molecules, and routes to achieving full biological integration.. Full details in the University publications repository. ...
Freeline to present new data at the 12th Annual Protein and Antibody Engineering Summit- Updated data on analytical technologies for determining the proportion of AAV capsids containing full-length vector genomes- Potentially increasing safety and efficacy in Freeline’s AAV delivery modelLondon, 30 October 202...
It is very unusual for a university to be leading a project like this as its normally industry-led, so its a great honour for us to be working with some of the top names in European industry, he said. The industry partners put in 50 percent of their own money, which is a sure sign that they take this seriously.. From the start weve made it clear that were not going to carry out research that is not meeting industrys needs. This project will only be a success if we are able to create what they need and can use.. The scientists will be using formal engineering methods to test the fault tolerance of each system and refining these in an industrial setting to ensure they meet the needs of an increasingly technological society.. Its often crucial that you can rely on these systems, explained Computing Science Professor Cliff Jones, who began his career working for IBM in the 1970s and has spent many years developing formal engineering methods for industry. For example, there is a device ...
Some commonly used factors include:. 6 Ms. (Wo)Man, Method, Materials, Measurement, Man, and Mother nature/environment. This set of factors is commonly used in the manufacturing/plant environment. In a health care setting these factors can be represented in a laboratory.. 8 Ps. Procedures, Processes, Policies, People, Promotion, Price, Product, and Place. This set of factors is commonly used in the administrative setting. In a health care setting these factors can be used to analyze patient data in the handover from one department to the next.. 4Ss. Skills, Surroundings, Suppliers, Systems. This set of factors is commonly used in the service industry. In a health care setting these factors can be used in an emergency room triage.. The 8Ps and 4Ss factors have been used in the service sector, especially in accounting, sales, customer service, and administration. These factors exist in many subsectors associated with health care delivery. For example, health insurance companies can use factors ...
Directed evolution has so far been used almost exclusively as a tool for engineering proteins. By mutation techniques such as site-directed mutagenesis, cassette-mutagenesis, random mutagenesis, and error prone PCR variants of protein functions have been generated and the libraries thus produced have been screened for their ability to perform a specific function. Recursive application of this procedure has been used successfully for the modification of physical and catalytic properties of enzymes such as pH optima, thermo-tolerance, solvent stability, stereoselectivity, catalytic activity and substrate specificity as well as toxicity resistance mechanisms in bacteria and the host range and stability of viruses.Traditional mutagenesis approaches for evolving new properties in enzymes have a number of limitations. These approaches are only applicable to genes or sequences that have been cloned and functionally characterized and that have a discrete function. Also, the traditional mutagenesis ...
Principal Investigator:MITSUI Yukio, Project Period (FY):1995 - 1996, Research Category:Grant-in-Aid for Scientific Research (B), Section:試験, Research Field:広領域