Role
Ivan Campeotto is a Visiting Senior Fellow in the School of Science and Technology.
Career overview
- Wellcome Trust ISSF – Early Career Research Fellow at the Leicester Institute of Structural and Chemical Biology.
- BTP Research Fellow at Pembroke College, University of Oxford.
- Research Associate at the University of Oxford.
- Research Associate at Imperial College London.
- Research Associate at King’s College London.
- PhD in protein crystallography at the Astbury Centre for Structural Molecular Biology, University of Leeds.
- Degree in Biotechnology at the University of Padua (Italy).
Research areas
Research interests in Campeotto’s group focus on understanding the mechanisms of infection of two parasites: Plasmodium falciparum and Trypanosoma cruzi, which are respectively the causative agents of malaria and Chagas disease.
Malaria infects approximately half a billion people worldwide and kills around 1 million people every year, three quarters of which are children under the age of 5 (WHO, 2016). There is no licensed vaccine and drug resistance has already been reported against artemisinin, currently the only leading therapy for malaria. The malaria projects target cyclic nucleotide binding proteins, protein kinases and other effector proteins, that are crucial for the establishment of the parasite infection and for the transmission to the mosquito. These projects are in collaboration with parasitologist Professor Rita Tewari (University of Nottingham).
Trypanosoma cruzi is endemic in South America, where approximately 10 million people are infected, causing approximately 20,000 deaths every year (WHO, 2016). The current therapies for Chagas disease produce severe side effects and are not effective against the chronic stage of the parasitic infection. The Trypanosoma cruzi projects are in collaboration with parasitologist Dr Martin Edreira at the University of Buenos Aires (Argentina) and aim to characterise novel T. cruzi proteins, which have been recently shown to play a key role in parasite development from a non-infective to an infective form.
In particular, Campeotto’s group is interested in elucidating the molecular details of host-pathogen interactions and in the key mechanisms that are responsible for the establishment of the parasite infection and for the development inside the host. To achieve this, a combination of structural and biophysical approaches is used, which combined with functional and in vivo studies, provides the ideal starting point for structure-guided drug design and a better understanding of parasite biology.
More recently, Campeotto’s research focused on a repertoire computational methods, which allowed him to design and to determine the crystal structure of an engineered variant of the Plasmodium falciparum RH5 protein, which is the leading candidate for the development of a blood-stage malaria vaccine (Campeotto et al., 2017- patent PCT/GB2017/052608).
A similar approach will be applied for the design of immunogens from other human pathogens through collaborations with leading experts. In particular, immunogenic molecules have been designed and engineered to be used to produce broadly neutralising antibodies against T. cruzi and to develop a Chagas vaccine. This project is in collaboration with Prof. John Kelly (London School of Hygiene and Tropical Medicine, UK), Prof. Mark Howarth (University of Oxford) and Prof. Lea Barfod (University of Copenhagen, Denmark).
External activity
- Editorial Board Member of Scientific Reports
- Honorary Fellow at the Leicester Institute of Structural and Chemical Biology, University of Leicester
- Member of the British Society for Parasitology
- Member of the Microbiology Society
- Member of the Biochemical Society
- Member of the working group 1 and working group 2 of the Collaborative Computational Project No. 4 (CCP4)
Publications
- Campeotto I, Galaway F, Mehmood S., Barfod LK, Quinkert D, Kotraiah V, Phares TW, Wright KE, Snijders AP, Draper SJ, Higgins MK, Wright GJ. 'The Structure of the Cysteine-Rich Domain of Plasmodium falciparum P113 Identifies the Location of the RH5 Binding Site'. mBio (2020) doi:10.1128/mBio.01566-20
- Warszawski S, Dekel E, Campeotto I, Marshall JM, Wright KE, Lyth O, Knop O, Regev-Rudzki N, Higgins MK, Draper SJ, Baum J, Fleishman SJ. 'Design of a basigin-mimicking inhibitor targeting the malaria invasion protein RH5.' Proteins (2019) doi: 10.1002/prot.25786
- Campeotto I**, Lebedev A, Schreurs AMM, Kroon-Batenburg LMJ, Lowe E, Phillips SEV, Murshudov GN, Pearson AR. Pathological macromolecular crystallographic data affected by twinning, partial-disorder and exhibiting multiple lattices for testing of data processing and refinement tools. Sci Rep. (2018) ** co-corresponding author http://dx.doi.org/10.1038/s41598-018-32962-6
- Campeotto I, Goldenzweig A, Davey J, Barford L, Marshall JM, Silk SE, Wright K, Draper SJ, Higgins MK, Fleishman SJ. ”One- step design of a stable variant of the malaria invasion protein RH5 for use as a vaccine immunogen” PNAS (2017). https://www.pnas.org/content/114/5/998
- Schuster CF, Bellows LE, Tosi T, Campeotto I, Corrigan RM, Freemont P, Gründling A. “The second messenger c-di-AMP inhibits the osmolyte uptake system OpuC in Staphylococcus aureus”. Sci Signal (2016). doi: 10.1126/scisignal.aaf7279
- Campeotto I, Zhang Y, Mladenov GM, Freemont SP and Grundling A. "Complex structure and Biochemical Characterization of the Staphylococcus aureus Cyclic Diadenylate Monophosphate (c-di-AMP)-binding Protein PstA, the Founding Member of a New Signal Transduction Protein Family. J. Biol. Chem. (2015). http://www.jbc.org/content/290/5/2888.long
- Thwaites T, Nogueira TA, Campeotto I, Silva PA, Grieshaber SS, Carabeo AR. "The Chlamydia Effector TarP Mimics the Mammalian Leucine-Aspartic Acid Motif of Paxillin to Subvert the Focal Adhesion Kinase during Invasion". J. Biol. Chem. (2014). doi: 10.1074/jbc.M114.604876
- Campeotto I, Percy GM, MacDonald TJ, Freemont SP, Grundling A. "A Structural and mechanistic insight into the Listeria monocytogenes two-enzyme lipoteichoic acid synthesis system". J. Biol. Chem. (2014). doi: 10.1074/jbc.M114.590570
- Daniels A, Campeotto I**, van der Kamp M, Bolt, A, Trinh CH, Phillips SE, Pearson AR, Nelson, A, Mulholland A, Berry, A. "The reaction mechanism of N-acetylneuraminic acid lyase revealed by a combination of crystallography, QM/MM simulation and mutagenesis.". ACS Chemical Biology (2014) **joint first author doi: 10.1021/cb500067z
- Corrigan M, Campeotto I, Jeganathan T, Roelofs JK, Lee TV, Grundling A. "Systematic identification of conserved bacterial c-di-AMP receptor proteins". PNAS (2013). doi: 10.1073/pnas.1300595110
- Campeotto I**and Acevedo-Rocha CG. “Hijacking nature – new approaches to unravel enzyme mechanisms and engineer improved biocatalysts”. EMBO Rep. (2013). **co-corresponding author doi: 10.1038/embor.2013.26
- Campeotto I, Bolt AH, Harman TA, Dennis C, Trinh CH, Phillips SE, Nelson A, Pearson AR, Berr A. "Structural insights into substrate specificity in variants of N-acetylneuraminic acid lyase produced by directed evolution". J. Mol. Biol. (2010). doi: 10.1016/j.jmb.2010.08.008
- Campeotto I, Carr SB, Trinh CH, Nelson AS, Berry A, Phillips SE, Pearson AR. "Structure of an Esherichia coli N-acetyl-D- neuraminic acid lyase mutant, E192N, in complex with pyruvate at 1.45 angstrom resolution". Acta Crystallogr F (2009). doi: 10.1107/S1744309109037403