C dot Fanutti at uea dot ac dot uk
Tel: +44 (0)1603 59 1272
1- Molecular dynamics of the outer membrane protein TolC.
Cellular membranes act as semipermeable barriers to ions and macromolecules and specialized mechanisms of transport are required for protein translocation. The outer membrane channel protein TolC plays a major role in Type I secretion of toxins and proteases, and in multidrug efflux systems of Gram-negative bacteria. Importantly, however, TolC is also involved in the import of a naturally occurring protein toxin, colicin E1, into susceptible bacterial cells. The mechanism of colicin E1 import across TolC channel is poorly understood.
We now wish to investigate the molecular dynamics of this protein by a combination of techniques that include X-ray crystallography and site-directed spin labelling electron paramagnetic resonance (SDSL-EPR) spectroscopy. A BBSRC grant has been awarded to support this research project. Several objectives are identified in this project, including the study of the uptake and transport mechanism of polypeptide substrates derived from colicin E1 across the TolC channel, and the study of dynamic intra- and inter-molecular changes of the outer membrane protein TolC purified and reconstituted in detergent or lipid bilayer in different experimental conditions.
This work is supported by collaborations with Prof. A. Thomson, School of Chemical Sciences and Pharmacy, and Dr A. Hemmings, School of Biological Sciences, at the University of East Anglia
2- Phage display and vaccine design.
The bacteriophage fd engineered to display T-helper and T-cytolytic epitopes from HIV-1 reverse transcriptase has been shown to modulate the immune response in vitro. However, very little is known about bacteriophage processing and presentation in antigen presenting cells. We now wish to explore the role of targeting molecules expressed on the minor coat protein in the uptake of bacteriophage fd in human macrophages and dendritic cells by confocal microscopy and established biochemical techniques. This work will exploit the imaging facilities at the School of Biological Sciences, University of East Anglia, and existing collaboration with School of Medicine and The Institute of Food Research.
3- The contribution of human metapneumovirus to respiratory infections in the Norfolk community.
This research study is being carried out in collaboration with Prof. Hunter in the School of Medicine and Prof. Sillis at the Norwich and Norfolk University Hospital. A small grant to support this research has been awarded by the John and Pamela Salter Charitable Trust.
4- Immune effectors and autoimmune diseases.
The role of erythropoietin is being investigated using an in vitro model of rheumatoid arthritis, in collaboration with Dr. Coussons at Anglia Ruskin University.
BioMedicine, Infection and Immunity
School of Medicine, Health Policy and Practice, UEA (2003-current)
Lectures and Seminars (Years 1-3)
Teaching involves primarily preparation and delivery of lectures and seminars to MB/BS medical degree students. Subjects taught include protein biochemistry and structural biology, protein-DNA interaction, control of gene expression, natural and acquired immunity, tolerance and autoimmunity, hypersensitive response, defence to microbial infections, inflammation and cancer immunology. As well as being involved in direct face-to-face teaching, I am also interested in the integration of information technology with teaching and learning in a problem based learning (PBL) medical course with the objective to develop practical skills in experimental science.
PBL Tutor for MB/BS students (Years 1-3)
Problem based learning (PBL) is a pedagogical method that combines theoretical conceptualisation of learning with experimental research-based practice. As a PBL tutor my responsibility is to facilitate and assist with the PBL group work. There are two sessions in each week (brainstorm and feedback) with 10 students and PBL tutorials run over 20 weeks in Year 1 and over 24 weeks in Years 2 and 3. Group work involves the analysis, identification of learning objectives and the study of clinical scenarios, thus gaining direct experience of evidence-based practice.
Student Selected Studies - Biochemistry Domain Coordination and Assessment (Year3)
The selected studies are integral part of each Unit (three Units in Year-3) and approximately 50 students carry out a research-based project in Biochemistry every year. Undergraduates are expected to expand their knowledge in a topic of their choice selected from a range of subjects covered during the specific Unit.
As a domain leader my main responsibility is concerned with the management, supervision and assessment of student research projects based on clinical cases and literature search required for the MBBS curriculum.
Supervisor of undergraduate medical research projects (MB/BS)
As project supervisor I am involved in the management of laboratory based research projects carried out by MB/BS students in the final year of their degree.
Immunology Theme Leader
The responsibility of this position is concerned with the overall design and delivery of the immunology course in the MB/BS curriculum. Specific learning objectives have been identified to cover natural and acquired immunity, tolerance and autoimmunity, hypersensitive response, defence to microbial infections, primary and secondary immunodeficiency disorders, inflammation and cancer immunology.
Rathbun, EA, Coussons, P and Fanutti, C (2011) Phage display of CTB enhances bacteriophage binding to human T lymphocytes. Implications for vaccine design. (Unpublished)
Coupland, L, Hunter, PR, Sillis, M and Fanutti, C (2010) Frequent involvement of Haemophilus influenzae in the infection with human Metaoneumovirus.
Coussons, PJ, Fanutti, C, Baig, S and Grant, R (2010) Recombinant human erythropoietin modulates tissue remodelling via a nitric oxides synthase-dependent process in an explant model of rheumatoid arthritis. (Unpublished)
Fanutti, C, Bawn, M, Rathbun, EA, Thomson, A, Coussons, PJ and MacMillan, F (2010) A study of the structure and dynamics of spin labelled TolC by EPR spectroscopy. (Unpublished)
MacMillan, F, Bawn, M, Rathbun, EA, Thomson, A, Coussons, PJ and Fanutti, C (2010) Conformational changes in the outer membrane protein TolC by site-directed spin labelling EPR. (Unpublished)
Coupland, L, Fanutti, C, Sillis, M and Hunter, PR (2009) Co-infection studies with human metapneumovirus. (Unpublished)
Howe, AC, Leinster, SJ and Fanutti, C (2009) Self and peer assessment of professional standards in a PBL - based Medical School. (Unpublished)
Coussons, PJ, Baig, S, Fanutti, C and Grant, R (2005) Novel tissue remodelling roles for human recombinant erythropoietin. Biochem Soc Trans, 33 (5). pp. 1129-1130.
Gaubin, M, Fanutti, C, Mishal, Z, Durrbach, A, De Berardinis, P, Sartorius, R, Del Pozzo, G, Guardiola, J, Perham, RN and Piatier-Tonneau, D (2003) Processing of filamentous bacteriophage virions in antigen-presenting cells targets both HLA class I and class II peptide loading compartments. DNA and Cell Biology, 22 (1). pp. 11-18.
Portefaix, J-M, Fanutti, C, Granier, C, Crapez, E, Perham, RN, Grenier, J, Pau, B and Del Rio, M (2002) Detection of anti-p53 antibodies by ELISA using p53 synthetic or phage-displayed peptides. Journal of Immunological Methods, 259 (1-2). pp. 65-75.
Guardiola, J, Chia, SH, De Berardinis, P, Sartorius, R, Fanutti, C, Perham, R and Del Pozzo, G (2001) Phage display of epitopes from HIV-1 elicits strong cytolytic responses in vitro and in vivo. Advances in Experimental Medicine and Biology, 495. pp. 291-298.
Sharff, A, Fanutti, C, Shi, J, Calladine, C and Luisi, B (2001) The role of the TolC family in protein transport and multi-drug efflux. European Journal Biochemistry, 268 (19). pp. 5011-5026.
De Berardinis, P, Sartorius, R, Fanutti, C, Perham, RN, Del Pozzo, G and Guardiola, J (2000) Phage display of peptide epitopes from HIV-1 elicits strong cytolytic responses. Nature Biotechnology, 18 (8). pp. 873-876.
Elliott, R and Fanutti, C (2008) Biochemistry and Molecular Biology. In: Biochemistry and Molecular Biology. Oxford University Press. ISBN 0199226717
De Berardinis, P, Sartorius, R, Fanutti, C, Perham, RN and Del Pozzo, G (2001) Phage display of epitopes from HIV-1 elicits strong cytolytic responses in vitro and in vivo. In: Progress in Basic and Clinical Immunology. Kluwer Academic/Plenum Publishers, pp. 291-298. ISBN 0306466562
Backstrom, M, Piatier-Tonneau, D, Coussons, P and Fanutti, C (2007) Display of cholera toxin B (CTB) enhances binding of bacteriophages to human T-cells. In: 2007 Miami Winter Symposium, Innate Immunity and Novel Vaccines, Miami.
Miles, S, Leinster, SJ, Howe, AC and Fanutti, C (2006) Self, Peer and Tutor assessment of professional behaviour: Designing a user-friendly form. In: ASME Conference: Multi-Source Feedback in Medical Education, London.
Vardakou, M, Rathbun, EA and Fanutti, C (2006) The mechanism of transport of the outer membrane protein TolC. In: HERCULES Specialised Courses on Structural Genomics, Grenoble, France.
Baig, S, Fanutti, C, Coussons, P and Grant, R (2005) Nitric oxide release and extracellular matrix turnover induced by recombinant human erythropoietin in a procine nasal cartilage explant model of rheumatoid arthritis. In: Biosciences Meeting, Glasgow, The Biochemical Society.
Baig, S, Fanutti, C, Coussons, PJ and Grant, R (2005) Nitric oxide release and extracellular matrix turnover induced by recombinant human erythropoietin in a porcine nasal cartilage explant model of rheumatoid arthritis. In: BioScience 2005, from genes to systems, Glasgow.
Fanutti, C, Coussons, PJ and Hemmings, AM (2005) Helical peptide found in the channel of the outer membrance protein TolC. In: Biosciences Meeting, Glasgow, The Biochemical Society.
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