Staff Profile
Dr Soren Nielsen
Research Associate
- Telephone: +44 (0) 191 208 3226
- Address: Biosciences Institute
Centre for Bacterial Cell Biology
Baddiley-Clark Building
Faculty of Medical Sciences
Newcastle University
Richardson Road
Newcastle upon Tyne
NE2 4AX
United Kingdom
Background
Introduction
I have many years international experience as a postdoctoral associate. For my Ph.D research I travelled from my native Denmark to Germany. Here I studied fatty acid metabolism in heart and in particular long chain fatty acid transport by a small and abundant intracellular fatty acid binding protein. I acquired valuable skills in protein purification techniques and cell culture as well as protein analysis by one and two-dimensional electrophoresis. I also became fluent in German and wrote my Ph.D thesis in the German language.
My first postdoctoral position was at University of Minnesota in Minneapolis, USA and I studied a membrane bound fatty acid transport protein in adipocytes. I acquired valuable skills in molecular biology and insight into American culture and worked hard for three years in the laboratory. I worked in a second short-term postdoctoral position at Texas A and M University in College Station, USA. Here I learned to work with baculovirus and express and purify proteins from insect cells. I have been a postdoctoral associate at Newcastle University since 1997 and here I have worked in three research areas. Hepatitis C virus (HCV) infects 150 million people worldwide of which 5 million are in Europe and 500,000 in the UK. I found that HCV circulates in blood associated with very low density lipoprotein (VLDL). These lipid particles are naturally secreted by the human liver to distribute triglyceride and cholesterol to organs and muscles in the body. HCV hijacks this pathway to produce HCV associated with apolipoproteins A-I, A-II, B, C-I and E. In patients with chronic HCV I also found immunoglobulins IgA, IgG1, IgG3 and IgM associated with the lipoproteins and with the virus. These results were published in the highest impact journals within the field of Virology and to date have received more than 400 citations. At Newcastle University I have also worked with RNA polymerases from yeast. Finally I worked at Newcastle University with humanized monoclonal antibodies. The knowledge I have obtained from working abroad benefits me every day, both when talking to people from different backgrounds and when making decisions and designing experiments in the laboratory.
Personal Website address
https://www.ncl.ac.uk/medical-sciences/research/institutes/biosciences/
I am member of the Biosciences Institute and my work contributes to the Microbes in Health and Disease theme.
Qualifications
Ph.D in Biochemistry from University of Munster, Germany, 1993
Masters Degree in Biochemistry from Aarhus University, Denmark, 1988
Masters Degree in Accounting from Business School Aarhus, Denmark, 1987
Bachelor Degree in Chemistry and Physics from Aarhus University, Denmark, 1985
Previous Positions
Postdoctoral associate at Newcastle University, England from 1997 to present (27 years)
Postdoctoral assistant at Texas A & M University, USA in 1996 (1/2 year)
Postdoctoral assistant at University of Minnesota, USA from 1993 to 1995 (3 years)
Ph.D student at Munster University in Germany from 1989 to 1993 (4 years)
Research assistant at Aarhus University in Denmark from 1985 to 1988 (4 years)
Memberships
Microbiology Society
Royal Society for Biology
Biochemical Society
British Society for Cell Biology
British Association for the Study of the Liver
American Association for the Advancement of Science
Honours and Awards
I became Fellow of the Royal Society of Biology (FRSB) in 2016
I received a Fellowship from HCV UK to attend the International HCV meeting in San Antonio, Texas (2008)
I received the Philip Hague Award from British Association for Study of the Liver (2005)
I received a Career Development Award from the Danish Research Foundation (1992-1993)
I received a Research Fellowship from the Danish Natural Sciences Research Council (1989-1993)
I received a Research Fellowship from the Danish Medical Research Council (1987-1988)
I am Chartered Scientist, CSci
Reviewer
In 2017, I have served as Reviewer for the journals Gut, Viral Hepatitis and Hepatology
Languages
I speak and write Danish, German and English
Informal Interests
I have run the Great North Run in Newcastle upon Tyne 20 times.
I have run several Marathons, including the Boston 100th anniversary Marathon, Twin Cities Marathon in Minneapolis, Aarhus Marathon, Cologne Marathon, London Marathon (2 times), Edinburgh Marathon (2 times) and Manchester Marathon (2 times).
Research
Research
I have been a postdoctoral associate at Newcastle University for 23 years. During this time I have worked in three different research groups. I have a wide range of experimental knowledge in biochemistry, molecular biology, density gradient ultracentrifugation, transcription, cell biology and protein purification. I am experienced in 1-D and 2-D gel electrophoresis, Western blotting and work with radioactivity. I also have several years experience with qPCR and ChIP analysis.
Research on RNA polymerases from S. cerevisiae
Research on Hepatitis C virus (HCV)
I have been a Wellcome Trust postdoctoral associate for 9 years, working on Hepatitis C virus. I purified the virus and characterized HCV C virus from infected human liver. I used my experience of iodixanol density gradient centrifugation and real time PCR to analyse the density profile of Hepatitis C virus from human serum and liver. I found the virus associates with very low density lipoprotein, VLDL. I also used the Electron Microscopy Unit at Newcastle University to obtain pictures of the HCV virus from density fractions and from size fractionated samples (See Figure below). I purified HCV lipo viro-particles from human liver by density gradients and by gel filtration. I found the virus is associated with apolipoproteins A-II, B and E from human blood. These associations with host apolipoproteins and antibodies may explain why Hepatitis C virus infection is chronic in more than 80% of infected people.
Research on humanized monoclonal antibodies
I was a postdoctoral associate in the research group of Dr. Edward Routledge at Newcastle University. The goal was to develop dimers of humanized monoclonal antibodies and test these antibodies in a mouse model of cancer of the blood, leukaemia. I gained knowledge in working with monoclonal antibodies and protein expression. I succeeded in prepared the humanized monoclonal antibodies and I did cross linking studies to improve the efficiency of the antibodies (see Figure below). The dimers of the antibodies were much better in killing cancer cells than the monomers and these results were published in the prestigious journal Blood.
Research on fatty acid binding protein from heart
I have worked 3 years as a postdoctoral assistant in USA and 4 years in Germany, studying for my Ph.D in Biochemistry. My research area was fatty acid binding proteins (FABPs). These are abundant cytosolic proteins in heart myocytes, mammary gland and adipocytes and they binds to and transport long chain fatty acids within cells. I isolated heart myocytes and could show that FABP is the second most abundant cytosolic protein, after myoglobin (see figure below).
Esteem Indicators
I was invited to give an oral presentation at the annual meeting in British Association for Study of the Liver (BASL) in September 2005. At the meeting at Kings College in London, I received the Philip Hague Award from BASL for the best abstract submitted to the annual meeting in the field of viral hepatitis.
I was invited to give an oral presentation at the annual meeting in BASL in September 2006 in Dublin.
I have been invited to give a 45 minutes seminar in January 2007 at the Institute Pasteur Hellenique in Athens, Greece. This was an honour for me which I am proud of. I gave a talk on my work with Hepatitis C virus and human lipoproteins at the meeting of American Association for Study of the Liver. This meeting was held in San Francisco, California and after the meeting I was invited by the Chairman of my session, Prof. T. Wakita to give a talk at his Institute for Virology in Tokyo, Japan and also spend one week in his group learning new techniques.
Industrial experience
I have collaborated with a company, Innogenetics in Ghent, Belgium, which provided me with 24 monoclonal antibodies to envelope glycoproteins of HCV. I used the antibodies in Western blotting and immunofluorescence. The characterization of these antibodies was of value to me because it gave me good reagents for use in HCV research and it was of value to the compagny because it improved their knowledge about the monoclonal antibodies.
Teaching
Undergraduate and postgraduate teaching
I have supervised three research project students. One of these, Daniel Lowther received a Distinction in his Master Degree on negative strand HCV RNA, a research project which I designed and supervised. I enjoy sharing my experience and giving help to students with their experiments.
Postgraduate Supervision
I have co-supervised Ph.D student Caroline Martin in collaboration with Prof. Geoffrey Toms. I have also been a co-supervisor for Ph.D student Siti Ibrahim.
Publications
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Articles
- Nielsen S, Zenkin N. Transcript assisted phosphodiester bond hydrolysis by eukaryotic RNA polymerase II. Transcription 2013, 4(5), 209-212.
- Nielsen S, Yuzenkova Y, Zenkin N. Mechanism of Eukaryotic RNA Polymerase III Transcription Termination. Science 2013, 340(6140), 1577-1580.
- Felmlee DJ, Sheridan DA, Bridge SH, Nielsen SU, Milne RW, Packard CJ, Caslake MJ, McLauchlan J, Toms GL, Neely RDG, Bassendine MF. Intravascular Transfer Contributes to Postprandial Increase in Numbers of Very-Low-Density Hepatitis C Virus Particles. Gastroenterology 2010, 139(5), 1774-1783.
- Bridge SH, Sheridan DA, Felmlee DJ, Nielsen SU, Thomas HC, Taylor-Robinson SD, Neely RDG, Toms GL, Bassendine M. Insulin resistance and low-density apolipoprotein B-associated lipoviral particles in hepatitis C virus genotype 1 infection. Gut 2010, 60(5), 680-687.
- Gias E, Nielsen SU, Morgan LAF, Toms GL. Purification of human respiratory syncytial virus by ultracentrifugation in iodixanol density gradient. Journal of Virological Methods 2008, 147(2), 328-332.
- Farquhar MJ, Harris HJ, Diskar M, Jones S, Mee CJ, Nielsen SU, Brimacombe CL, Molina S, Toms GL, Maurel P, Howl J, Herberg FW, Van IJzendoorn SCD, Balfe P, McKeating JA. Protein kinase A-dependent step(s) in hepatitis C virus entry and infectivity. Journal of Virology 2008, 82(17), 8797-8811.
- Grove J, Nielsen SU, Zhong J, Bassendine MF, Drummer HE, Balfe P, McKeating JA. Identification of a residue in hepatitis C virus E2 glycoprotein that determines scavenger receptor BI and CD81 receptor dependency and sensitivity to neutralizing antibodies. Journal of Virology 2008, 82(24), 12020-12029.
- Nielsen SU, Bassendine MF, Martin C, Lowther D, Purcell PJ, King BJ, Neely D, Toms GL. Characterization of hepatitis C RNA-containing particles from human liver by density and size. Journal of General Virology 2008, 89(10), 2507-2517.
- Martin C, Nielsen SU, Ibrahim SF, Bassendine MF, Toms GL. Binding of liver derived, low density hepatitis C virus to human hepatoma cells. Journal of Medical Virology 2008, 80(5), 816-823.
- Nielsen SU, Bassendine MF, Burt AD, Martin C, Pumeechockchai W, Toms GL. Association between hepatitis C virus and very-low-density lipoprotein (VLDL)/LDL analyzed in iodixanol density gradients. Journal of Virology 2006, 80(5), 2418-2428.
- Nielsen SU, Bassendine MF, Burt AD, Bevitt DJ, Toms GL. Characterization of the genome and structural proteins of hepatitis C virus resolved from infected human liver. Journal of General Virology 2004, 85(6), 1497-1507.
- Nielsen SU, Routledge EG. Human T cells resistant to complement lysis by bivalent antibody can be efficiently lysed by dimers of monovalent antibody. Blood 2002, 100(12), 4067-4073.
- Nielsen S, Bassendine M, Burt A, Toms G. Characterization of the structural proteins of HCV isolated from human liver. Journal of Hepatology 2002, 36(s1), 87 abstract no. 301.
- Nielsen S, Pumeechockchai W, Burt A, Bassendine M, Toms G. Characterization of HCV RNA particles from the serum of a patient with common variable immunodeficiency on isotonic iodixanol (optiprep) gradients. Association with apolipoprotein-B100. Journal of Hepatology 2002, 36(s1), 87 abstract no. 301.
- Nielsen SU, Rump R, Hojrup P, Roepstorff P, Spener F. Differentiational regulation and phosphorylation of the fatty acid-binding protein from rat mammary epithelial cells. Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1994, 1211(2), 189-197.
- Nielsen S, Spener F. Fatty acid-binding protein from rat heart is phosphorylated on Tyr19 in response to insulin stimulation . Journal of Lipid Research 1993, 34(8), 1355-1366.
- Brodersen R, Andersen S, Vorum H, Nielsen S, Pedersen AO. Multiple fatty acid binding to albumin in human blood plasma. European Journal of Biochemistry 1990, 189(2), 343-349.
- Celis JE, Madsen P, Nielsen S, Ratz GP, Lauridsen JB, Celis A. Levels of synthesis of primate-specific nuclear proteins differ between growth-arrested and proliferating cells. Experimental Cell Research 1987, 168(2), 389-401.
- Nielsen SU, Celis A, Ratz GP, Celis JE. Identification of two human phosphoproteins (dividin and IEF 59dl) that are first detected late in G1 near the G1/S transition border of the cell cycle. Leukemia 1987, 1(1), 69-77.
- Celis JE, Madsen P, Nielsen S, Rasmussen HH. Expression of cyclin (PCNA) and the phosphoprotein dividin are late obligatory events in the mitogenic response. Anticancer Research 1987, 7, 605-616.
- Pallesen G, Nielsen S, Celis JE. Characterization of a monoclonal antibody (BG3C8) that reacts with basal cells of stratified epithelia. Histopathology 1987, 11(6), 591–601.
- Celis JE, Madsen P, Andersen I, Andersen P, Vayssiere JL, Croizat B, Thiessen H, Nielsen S. Anti-mitochondrial protein antibodies in a serum from a patient with systemic lupus erythematosus: Specificity and comparison with other anti-mitochondrial antibodies. Electrophoresis 1987, 8(5), 238–243.
- Celis JE, Nielsen S. Proliferation-sensitive nuclear phosphoprotein "dividin" is synthesized almost exclusively during S phase of the cell cycle in human AMA cells. Proceedings of the National Academy of Sciences 1986, 83(21), 8187-8190.
- Celis JE, Madsen P, Nielsen S, Celis A. Nuclear patterns of cyclin (PCNA) antigen distribution subdivide S-Phase in cultured cells - some applications of PCNA antibodies. Leukemia Research 1986, 10(3), 237-249.
- Madsen P, Nielsen S, Celis JE. Monoclonal antibody specific for human nuclear proteins IEF 8Z30 and 8Z31 accumulates in the nucleus a few hours after cytoplasmic microinjection of cells expressing these proteins. The Journal of Cell Biology 1986, 103(6, pt.1), 2083-2089.
- Celis JE, Gesser B, Small JV, Nielsen S, Celis A. Changes in the levels of human tropomyosins IEF 52, 55 and 56 do not correlate with the loss of actin cables observed in SV 40 transformed MRC-5 fibroblasts. Protoplasma 1986, 135(1), 38-49.
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Conference Proceedings (inc. Abstracts)
- Bridge SH, Sheridan DA, Felmlee DJ, Nielsen SU, Neely RDG, Toms GL, Bassendine MF. Insulin resistance correlates with low density hepatitis C virus particles in genotype 1 infection. In: Journal of Hepatology: 45th Annual Meeting of the European Association for the Study of Liver. 2010, Vienna, Austria: Elsevier BV.
- Felmlee D, Bridge S, Sheridan DA, Nielsen SU, Toms G, Neely D, Bassendine M. Large and Buoyant Hepatitis C Virus (HCV) Particles Surge after Patients Consume a High-Fat Meal. In: Hepatology: 60th Annual Meeting of the American Association for the Study of Liver Diseases. 2009, Boston, Massachusetts, USA: John Wiley & Sons, Inc.
- Bridge S, Sheridan DA, Felmlee D, Nielsen SU, Neely D, Toms GL, Bassendine MF. Apolipoprotein B Associated Hepatitis C Virus (HCV): A Minority of Total Viral Load in Patients with Chronic HCV. In: Hepatology: 60th Annual Meeting of the American Association for the Study of Liver Diseases. 2009, Boston, Massachusetts, USA: John Wiley & Sons, Inc.
- Welsh S, Nielsen SU, Ward AC, Bassendine MF. Analysis of reactivity of PBC sera with bacterial antigens modified by xenobiotic exposure. In: 43rd Annual Meeting of the European Association for the Study of the Liver. 2008, Milan, Italy: Journal of Hepatology: Elsevier.
- Nielsen S, Bassendine M, Neely D, Ibrahim S, Toms G. Characterization of hepatitis C virus associated with very low density lipoprotein (VLDL) in infected human serum and liver. In: 21st Annual Medical and Scientific Meeting of HEART UK. 2007, Edinburgh, Scotland: Atherosclerosis, Elsevier.
- Nielsen SU, Bossendine M, King BJ, Neely D, Toms GL, Liver Research Group. Characterization of hepatitis C RNA containing particles from human liver by density and morphology. In: 58th Annual Meeting of the American Association for the Study of Liver Diseases. 2007, Boston, MA: Hepatology, John Wiley.
- Nielsen SU, Bassendine M, Martin C, Ibrahim S, Toms GL, Neely D. Development of a purification procedure for native hepatitis C virus from human liver. In: Hepatology:57th Annual Meeting of the American Association for the Study of Liver Diseases. 2006, Boston, Massachusetts, USA: John Wiley & Sons, Inc.
- Nielsen SU, Burt AD, Martin C, Bassendine MF, Toms GL. Human hepatitis C virus RNA circulates predominantly in VLDL-like lipo-viral-particles. In: Atherosclerosis: 19th Annual Medical and Scientific Meeting of HEART UK. 2005, University of Glamorgan, Pontypridd, WALES: Elsevier Ireland Ltd.
- Nielsen SU, Burt AD, Martin C, Bassendine M, Toms G. Hepatitis C virus RNA circulates predominantly in VLDL-like lipo-viral particles. In: Hepatology: 56th Annual Meeting of the American Association for the Study of Liver Diseases. 2005, San Francisco, California, USA: John Wiley & Sons, Inc.
- Martin C, Nielsen SU, Bassendine MF, Toms GL. Hepatitis C virus lipo-viro-particle interactions with human hepatocytes and inhibition of of binding. In: Hepatology: 56th Annual Meeting of the American Association for the Study of Liver Diseases. 2005, San Francisco, California, USA: John Wiley & Sons, Inc.
- Nielsen S, Bassendine MF, Burt A, Toms GL. Characterisation of the genome and structural proteins of beta-lipoprotein associated HCV extracted from infected human liver. In: Gut: Annual Meeting of the British Association for the Study of the Liver. 2003, Newcastle upon Tyne, UK: BMJ Group.
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Editorial
- Nielsen S, Zenkin N. Response to Comment on "Mechanism of eukaryotic RNA polymerase III transcription termination". Science 2014, 345(6196), 524-524.
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Review
- Bassendine MF, Nielsen SU, Bridge SH, Felmlee DJ, Sheridan DA, Packard CJ, Neely RD. Hepatitis C virus and atherosclerosis: A legacy after virologic cure?. Clinics and Research in Hepatology and Gastroenterology 2017, 41(1), 25-30.