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  • 1. R & D Systems: Tools for Cell Biology Research R&D Systems is please to offer internship opportunities for college students interested in the biological sciences. These internships are designed to provide training and research experience at R&D Systems for students who want to develop their skills in a professional, industrial environment. These are paid internship positions and have an hourly wage of $14.00. All positions are full-time, with the 40 hours generally worked between the hours of 8:00 – 5:00, Monday through Friday. Internships are awarded for an eleven-week period starting June 7th and ending August 20th. Eligibility Requirements Eligible college students must be a Junior standing, which will be determined by the amount of completed college credits at the application deadline, hold a GPA of 3.0 or better in their major science courses, and have declared their major in biology, chemistry or a related field. How to Apply Applications must be postmarked by March 12, 2010. Interviewed applicants will be notified no later than May 8th of internship selections. Required application materials include a cover letter, resume, official transcripts, and names & contact information for two professional or academic references. A letter of recommendation from one of the references listed would also be considered, but is optional. Please list your top choices for placement in the following: • Stem Cell Product Development • Validation of Cell Bank Consistency for Monoclonal Antibody Production • Optimization of Bioassay Parameters • Characterization of Size Exclusion Chromatography Elution Patterns for Monoclonal Antibodies • Characterization of Monoclonal Antibody Microheterogeneity • Development of Bead-based Method for In vitro Activation &Differentiation of T Cells • Bioinformatics • Protein Process Development • Antibody Array Products • Enzymes • Cell Culture Development—Optimization of Cell Growth for Recombinant Protein Expression • Optimization of Recombinant Protein Expression *A brief description of each of these projects is below Please mail application materials to: R&D Systems, Inc. Attn: Internship Program 614 McKinley Place NE Minneapolis, MN 55413-2610 Questions can be directed to (612) 656-4555 or hr@rndsystems.com
  • 2. Stem Cell Product Development Department: Antibody Application Stem cells have been discovered in many different organs and tissues. Recent interest in these cells has soared due to their multi-lineage differentiation and in vivo expansion potential, immunosuppressive properties, and ability to secrete bioactive factors. These cells serve as promising candidates for tissue engineering and cell-based therapies. We are currently focusing on the development of research reagents for multipotent stem cells including neural and mesenchymal stem cells. The intern for this project will contribute to the development of products in this area, working closely with the primary investigator in charge of the project. The major techniques employed will include, but and are not limited to, cell culture, flow cytometry, immunocytochemistry, and colony-forming cell assays. This internship is an excellent opportunity for a student to gain scientific experience in an industrial setting. The intern will be expected to give a formal Validation of Cell Bank Consistency for Monoclonal Antibody Production Department: Cell Culture Production One or more properties of a cell line are likely to change during an extended period of continuous passage. Due to a native feature known as genetic instability of a hybridoma, and post-translational modifications that take place in host cells, the biochemical structure and biological function of a protein can be altered. This can make it difficult to consistently produce a monoclonal antibody from a selected hybridoma. In order to ensure consistency, it is necessary to cryopreserve and characterize a reference stock of cells. Following a defined passage interval of cells from this stock, cell cultures are discarded and the cryopreserved stock is used to reinitiate fresh cultures. To ensure continuity of production from a cultured cell line, a two-tiered cell bank system is typically prepared. This consists of a master cell bank (MCB) of 50–400 ampoules and working cell banks, each derived in an identical manner from one ampoule of the MCB. The MCB is created from a single cell source called a pilot cell bank, which is selected for monoclonal antibody production. The first step in a quality manufacturing system is to establish consistent pilot, master, and working cell banks. The proposed research project is designed to test the consistency among the three established cell banks by determining 1) the clonality (homogeneity) and specific productivity rate (yield) of each bank, and 2) the specificity (unique function) and potency (titer) of the antibodies produced from each bank. The intern selected for this project should have basic training and knowledge of cell culture, and biochemical and immunological techniques including protein separation by flow chromatography (size exclusion and ion-exchange), isoelectric focusing (IEF), isotype-specific enzyme-linked immunosorbent assay (ELISA), and Western blotting. The intern will be expected to give a formal presentation on his or her work at the conclusion of the summer project.
  • 3. Optimization of Bioassay Parameters Department: Bioassay Protein-specific cell-based assays are essential for monitoring the quality of our products. The intern will work on the development of bioassays to test the activities of specific recombinant proteins under the supervision of research scientists. This position requires knowledge of proteins and cell biology, and previous training in general laboratory techniques such as pipetting and reagent preparation. Knowledge of aseptic techniques is desirable. The intern will be expected to give a formal presentation on his or her work at the conclusion of the summer project. Characterization of Size Exclusion Chromatography Elution Patterns for Monoclonal Antibodies Department: Quality Control Size exclusion chromatography (SEC) has routinely been used to detect aggregates and fragments present in antibody preparations. Accurate identification of these forms relies heavily on the establishment of reference standards for normal SEC elution patterns. For this project, the intern will analyze monoclonal antibody SEC data to identify the typical and atypical patterns for different types and species of antibodies. The intern will use statistical techniques to establish common SEC pattern parameters including retention time, asymmetry, and resolution. The intern will examine factors that affect the accuracy of SEC data including column lifespan, cleaning frequency, elution buffer composition, and quantitation limit. To understand atypical SEC patterns, the intern will conduct an experimental study designed to identify the underlying causes of these patterns such as antibody modifications and/or its intrinsic properties. Once the causes of atypical SEC elution patterns have been identified, the intern will test methods to eliminate these patterns. Throughout the project, the intern will learn useful analytical techniques such as SEC, SDS-PAGE, and Western blotting, while also gaining experience in project design, data analysis, and scientific presentation. The intern will be expected to give a formal presentation on his or her work at the conclusion of the summer project. Characterization of Monoclonal Antibody Microheterogeneity Department: Antibody Production Monoclonal antibody microheterogeneity can be attributed to glycosylation, oxidation, mutation, phosphorylation, amino terminal modifications (e.g., to pyroglutamate), incomplete processing of the C-terminus, and asparagine (Asn) deamidation. These variations in protein composition occur in many types of proteins and can impact their activity and stability. Using weak cation exchange chromatography as one tool, the intern will characterize microheterogeneities responsible for lot-to-lot variabilities and their effects on antibody binding affinity and protein stability. The intern will be expected to give a formal presentation on his or her work at the conclusion of the summer project. Development of Bead-based Method for In-Vitro Activation and Differentiation of T-Cells Department: Monoclonals Antibodies presented on beads are often used for in vitro activation of T cells. We are
  • 4. interested in using R&D Systems large collection of antibodies and recombinant proteins to make new bead-based products that are designed to activate a variety of cell subsets. Proteins and antibodies can be bound to the surface of polystyrene beads, or they can be loaded onto biodegradable cage-type beads made from polylactoglycolide. The intern will focus on the production of antibody-coated beads, characterization of antibody- coated bead stability, and analysis of batch-to-batch reproducibility. Methods used will include flow cytometry and standard T cell activation assays to characterize the performance of the antibody-coated beads. Upon the conclusion of the project, the intern will have gained an understanding of the general immunological assays used in T cell activation, general principles of flow cytometry, and the processes used to explore the development of new products using our monoclonal antibodies. The intern will be expected to give a formal presentation on his or her work at the conclusion of the summer project. Bioinformatics Department: Bioinformatics Bioinformatics is a growing computer-based discipline that plays an increasingly important role at many biotechnology companies including R&D Systems. It is expected that the candidates applying for this internship will have some degree of experience in database development and programming as this position will be coding intensive from the first day. The intern will use and develop her or his skills in this area, while building new tools and methods for product development. Possible projects include integrating automated analysis tools into our product development pipeline and mapping literature references to biological objects. The intern selected for this position will work under the direction of the principal bioinformaticist at R&D Systems. Currently, the bioinformatics group utilizes open source technology. This includes Linux, Mysql, Perl, and Ruby-on- Rails. In addition to programming experience, it is also preferred that the intern has some coursework in biology, but this is not required. The intern will be expected to give a formal presentation on his or her work at the conclusion of the summer project. Protein Process Development Department: Protein Development We are currently conducting several projects that involve important cytokine families including the TGF-b, TNF-a, FGF, VEGF, Wnt, adhesion molecule, and neuronal protein families. Molecules from these families play important roles in development (embryonic through adult), inflammation, and immune responses, suggesting that they may be useful for treating diseases. The intern will participate in developing methods for small-scale purification and refolding of recombinant proteins expressed in vertebrate cells (mammalian and insect cells) and bacteria. Based on the properties of the proteins (amino acid sequences, pI, structures, etc.), the intern will determine the best method(s) to obtain active proteins. The intern will learn about protein structure, how to decide on purification strategies based on protein structure, and commonly used purification methods such as gel electrophoresis, protein measurement, centrifugation, and column chromatography, working under the supervision of scientists and research associates. The intern will be expected to give a f formal presentation on his or her work at the conclusion of the summer project.
  • 5. Antibody Array Products Department: Intracellular Receptor-tyrosine kinases (RTKs) are transmembrane proteins that have been implicated in various cancers and are considered to be targets for drug design. RTKs are activated by phosphorylation on intracellular tyrosine residues. Therefore, methods that can be used to rapidly identify the effects of RTK inhibitors or antibodies that modify RTK phosphorylation may be useful tools for drug screening. R&D Systems Proteome Profiler™ and Proteome Profiler 96 Antibody Arrays can be used analyze multiple proteins in a single sample using a chemiluminescent detection method. The array group in the intracellular department is seeking an intern to investigate the effects of a series of kinase inhibitors on RTK phosphorylation utilizing the Proteome Profiler and Proteome Profiler 96 Antibody Arrays. In addition, the intern will explore the use of alternate detection methods for these multi-analyte profiling assays such as fluorescence. Results from the Proteome Profiler and Proteome Profiler 96 Kits will be compared to the single analyte DuoSet® IC ELISA Kits. This project will expose the intern to a number of scientific methods and techniques including mammalian cell culture, array product manufacturing, assaying protein levels using Duoset IC ELISAs and Proteome Profiler or Proteome Profiler 96 kits, and data analysis from these experiments. The intern will be expected to give a formal presentation on his or her work at the conclusion of the summer project. Enzymes Department: MMP Group Catalyzing chemical reactions in our bodies, enzymes are essential for transcription, translation, protein processing, and post-translational modifications. Enzymes play important roles in many physiological processes such as blood coagulation, wound healing, and embryonic development. They are also important targets in the diagnosis and treatment of serious diseases such as HIV, cancer, anthrax, Alzheimer’s disease, and the H1N1 pandemic. Our goal is to develop high quality enzyme reagents to facilitate basic research and disease intervention. The intern will not only gain a basic knowledge of enzymes and inhibitors, but valuable research experience in this area from a top team of scientists. Projects will involve protein purification, enzyme characterization, and antibody analysis. The techniques employed may include column chromatography, enzyme and inhibitor assays, SDS-PAGE, Western blotting, immunoprecipitation, neutralization, and ELISAs. In the course of the summer, the intern will also learn how to design experiments, document procedures, and interpret results. At the end of the summer, the intern will be expected to give a formal presentation to the company summarizing his/her achievement. Cell Culture Development-Optimization of Cell Growth for Recombinant Protein Expression Department: Cell Culture Development Optimal cell growth is essential for recombinant protein expression in mammalian cells. The goal of this project is to optimize the formulation of media used for growing selected cell lines such as NS0, CHO, and HEK293, and to identify feeding strategies that optimize the expression of recombinant proteins. The summer intern is expected to have a
  • 6. basic knowledge of cell physiology and media composition. She or he will be asked to conduct experiments to test various cell culture conditions, perform Western blot analysis, and run other protein assays. The intern will also be responsible for analyzing data and properly reporting results in both a written and an oral format. The selected intern will be guided by a motivated team of scientists and research associates. Students in bioprocess, biochemical engineering, or cell biology-related disciplines are encouraged to apply. The intern will be expected to give a formal presentation on his or her work at the conclusion of the summer project. Optimization of Recombinant Protein Expression Department: Cell Culture Development The intern will work on the development of new techniques for protein expression in Escherichia coli or insect cell culture. This will involve one or more of the following: 1) cloning genes under new or modified promoters, 2) modifying genes at the level of their DNA sequence, or 3) optimizing media formulations and cell culture conditions. The selected intern will be guided by a scientist/senior research associate in the Cell Culture Department. The intern will be expected to have previous experience with general laboratory techniques such as pipetting and preparing solutions. In addition, knowledge of aseptic techniques in microbiology, or experience in molecular biology (i.e. methods for DNA manipulation) will be useful. The intern will be responsible for preparing solutions and buffers, cloning, culturing cells for the production of recombinant proteins, SDS-PAGE, Western blotting, and data analysis. The intern will be expected to give a formal presentation on his or her work at the conclusion of the summer project.

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