Polizzi, Karen - Imperial College London - Department of Life Sciences, Biochemistry and Biotechnology

研究领域

Biopharmaceutical Processing Biopharmaceuticals, or protein therapeutics, are the fastest growing sector of the pharmaceutical industry. Our work in biopharmaceutical processing aims to increase the expression level of heterologous proteins in yeast and mammalian cells. Metabolic Markers of High Productivity Cells This project aims to develop FRET-based sensors for important primary metabolites that correlate well with the level of protein production in cell lines. These can then be used as a surrogate assays in the high throughput screening of cell for enhanced productivity. Biosensors of Cell Stress High levels of protein overexpression can cause cell stress from amino acid starvation, the accumulation of unfolded or misfolded proteins, and various other mechanisms. We are developing biosensors of these stress response pathways and developing synthetic genetic circuits aimed at overcoming cell stress. Cellular Cooperativity We are creating synthetic organisms that work together to accomplish goals in biopharmaceutical processing, such as providing nutrients on-demand to growing cultures. Neurodegeneration and Ageing Protein secretion, trafficking, and misfolding are also involved in neurodegeneration from diseases such as Alzheimer''s and Parkinson''s and from ageing in general. Unvraveling the role of the ER stress response in neurodegeneration With Dr Cleo Kontoravdi (Chemical Engineering), we are trying to understand what role endoplasmic reticulum stress plays in neuronal cell loss in Alzheimer''s disease. Tools for Synthetic Biology We are also involved in ongoing work to add to the tools available for synthetic biology in multiple projects. This work is in collaboration with Dr Mauricio Barahona (Bioengineering), Dr Guy-Bart Stan, and researchers at Edinburgh, Leeds, Sheffield, and UCL.

近期论文

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Sou SN, Jedrzejewski PM, Lee K, Sellick C, Polizzi KM, Kontoravdi Cet al., Model-based investigation of intracellular processes determining antibody Fc-glycosylation under mild hypothermia, Biotechnology and Bioengineering, ISSN: 1097-0290 Aw R, Polizzi KM, 2016, Liquid PTVA: a faster and cheaper alternative for generating multi-copy clones in Pichia pastoris, MICROBIAL CELL FACTORIES, Vol: 15, ISSN: 1475-2859 Klymenko OV, Shah N, Kontoravdi C, Royle KE, Polizzi KMet al., 2016, Designing an Artificial Golgi Reactor to Achieve Targeted Glycosylation of Monoclonal Antibodies, AICHE JOURNAL, Vol: 62, Pages: 2959-2973, ISSN: 0001-1541 Moore SJ, Lai HE, Kelwick RJ, Chee SM, Bell DJ, Polizzi KM, Freemont PSet al., 2016, EcoFlex: A Multifunctional MoClo Kit for E. coli Synthetic Biology., ACS Synth Biol, Vol: 5, Pages: 1059-1069 del Val IJ, Polizzi KM, Kontoravdi C, 2016, A theoretical estimate for nucleotide sugar demand towards Chinese Hamster Ovary cellular glycosylation, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322 Sou SN, Sellick C, Lee K, Mason A, Kyriakopoulos S, Polizzi KM, Kontoravdi Cet al., 2015, How Does Mild Hypothermia Affect Monoclonal Antibody Glycosylation?, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 112, Pages: 1165-1176, ISSN: 0006-3592 Behjousiar A, Constantinou A, Polizzi KM, Kontoravdi Cet al., 2014, FIBS-enabled Noninvasive Metabolic Profiling, Jove-Journal of Visualized Experiments, ISSN: 1940-087X Goers L, Freemont P, Polizzi KM, 2014, Co-culture systems and technologies: taking synthetic biology to the next level, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 11, ISSN: 1742-5689 Jedrzejewski PM, del Val IJ, Constantinou A, Dell A, Haslam SM, Polizzi KM, Kontoravdi Cet al., 2014, Towards Controlling the Glycoform: A Model Framework Linking Extracellular Metabolites to Antibody Glycosylation, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 15, Pages: 4492-4522, ISSN: 1422-0067 Polizzi KM, Kontoravdi C, 2014, Genetically-encoded biosensors for monitoring cellular stress in bioprocessing, Current Opinion in Biotechnology, Vol: 31, Pages: 50-56, ISSN: 1879-0429 Arpino JAJ, Hancock EJ, Anderson J, Barahona M, Stan G-BV, Papachristodoulou A, Polizzi Ket al., 2013, Tuning the dials of Synthetic Biology, MICROBIOLOGY-SGM, Vol: 159, Pages: 1236-1253, ISSN: 1350-0872 Aw R, Polizzi KM, 2013, Can too many copies spoil the broth?, MICROBIAL CELL FACTORIES, Vol: 12, ISSN: 1475-2859 Constantinou A, Polizzi KM, 2013, Opportunities for bioprocess monitoring using FRET biosensors, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 41, Pages: 1146-1151, ISSN: 0300-5127 Goers L, Kylilis N, Tomazou M, Wen KY, Freemont P, Polizzi Ket al., 2013, Engineering Microbial Biosensors, Editors: Harwood, Wipat, Publisher: ELSEVIER ACADEMIC PRESS INC, Pages: 119-156, ISBN: 978-0-12-417029-2 Kyriakopoulos S, Polizzi KM, Kontoravdi C, 2013, Comparative analysis of amino acid metabolism and transport in CHO variants with different levels of productivity, JOURNAL OF BIOTECHNOLOGY, Vol: 168, Pages: 543-551, ISSN: 0168-1656 Polizzi KM, 2013, What is synthetic biology?, Methods Mol Biol, Vol: 1073, Pages: 3-6 del Val IJ, Kyriakopoulos S, Polizzi KM, Kontoravdi Cet al., 2013, An optimized method for extraction and quantification of nucleotides and nucleotide sugars from mammalian cells, ANALYTICAL BIOCHEMISTRY, Vol: 443, Pages: 172-180, ISSN: 0003-2697 Behjousiar A, Kontoravdi C, Polizzi KM, 2012, In Situ Monitoring of Intracellular Glucose and Glutamine in CHO Cell Culture, PLOS ONE, Vol: 7, ISSN: 1932-6203 Chen N, Koumpouras GC, Polizzi KM, Kontoravdi Cet al., 2012, Genome-based kinetic modeling of cytosolic glucose metabolism in industrially relevant cell lines: Saccharomyces cerevisiae and Chinese hamster ovary cells, BIOPROCESS AND BIOSYSTEMS ENGINEERING, Vol: 35, Pages: 1023-1033, ISSN: 1615-7591 Chen N, del Val LJ, Kyriakopoulos S, Polizzi KM, Kontoravdi Cet al., 2012, Metabolic network reconstruction: advances in in silico interpretation of analytical information, CURRENT OPINION IN BIOTECHNOLOGY, Vol: 23, Pages: 77-82, ISSN: 0958-1669