The Insect Pathogenicity of Cordyceps militaris - a molecular, metabolic, ecological, and phylogenetic study
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Pharmacy
Abstract
Cordycepin, or 3'-deoxyadenosine, is a secondary metabolite secreted by the cosmopolitan entomopathogenic "caterpillar fungus" Cordyceps millitaris and closely related species. The metabolite is well known for its anti-inflammatory effects and thus has been used as both a traditional Chinese medicine for centuries and a focus of pharmacological research in recent years. However, studies on the ecological roles of cordycepin and other secondary metabolites in the infection of the insect larval host and the involvement of these on the sexual development which occurs following this process are in their infancy. Culture degeneration, a phenomenon observed in a broad range of ascomycete fungi, is the loss of ability to develop sexually and perform parts of secondary metabolism following subsequent subculturing in the vegetative state. This is a significant problematic issue in cordycepin production from laboratory and industrial-based cultures.
Here, a Chinese strain of Cordyceps militaris, CM2 (MycoMedica) with high cordycepin production was successively sub-cultured on potato dextrose agar. Targeted analysis of cordycepin and associated metabolite pentostatin by liquid chromatography (LC)-coupled mass spectrometry (MS), combined with a gene expression analysis using RT-qPCR provided evidence of a link between phenotypes and gene expression of both sexual development and secondary metabolite biosynthesis. Cordycepin production was greatly reduced in degenerated, multiply-subcultured samples; although production was partially restored following long-term transfer of these to a new media type based on the host substrate (silk pupa powder agar). Significant decreases in the expression of a sexual development gene, as well as cordycepin and related biosynthesis genes were also detected. Untargeted LC-MS analysis was performed to compare degenerated and non-degenerated strains.
Here, a Chinese strain of Cordyceps militaris, CM2 (MycoMedica) with high cordycepin production was successively sub-cultured on potato dextrose agar. Targeted analysis of cordycepin and associated metabolite pentostatin by liquid chromatography (LC)-coupled mass spectrometry (MS), combined with a gene expression analysis using RT-qPCR provided evidence of a link between phenotypes and gene expression of both sexual development and secondary metabolite biosynthesis. Cordycepin production was greatly reduced in degenerated, multiply-subcultured samples; although production was partially restored following long-term transfer of these to a new media type based on the host substrate (silk pupa powder agar). Significant decreases in the expression of a sexual development gene, as well as cordycepin and related biosynthesis genes were also detected. Untargeted LC-MS analysis was performed to compare degenerated and non-degenerated strains.
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M008770/1 | 01/10/2015 | 31/10/2024 | |||
| 1945077 | Studentship | BB/M008770/1 | 01/10/2017 | 30/09/2021 |
| Description | I have been studying an important fungal pathogen of insects, particularly caterpillars - Cordyceps militaris. Close relatives of this fungus have been used in biological control of insect pests. However, Cordyceps militaris differs from these in its capacity to infect insects in the sexual stage of its life cycle (unlike, for instance Beauveria bassiana). It is well known also for its production of cordycepin (3'-deoxyadenosine), which is known for a range of pharmacological effects, especially anti-inflammatory activities. This compound works as a polyadenylation inhibitor in cells, targeting specific mRNAs and hence genes. I am studying the role of cordycepin in insect parasitism of this fungus, and hence also the sexual life cycle of the fungus. To address the key questions, I have used approaches including fungal culture, mass spectrometry (to detect and quantify cordycepin), gene expression analyses and experiments on caterpillar host models. I have found much evidence of the role of cordycepin as a deliberate hindrance of the insect immune system (which bears similarities to the mammalian immune system) - in order to allow the fungus to establish infection. I have also found evidence that cordycepin production is directly linked with the traits of the sexual cycle and associated gene expression of the fungus. This is currently being written into a journal paper. |
| Exploitation Route | This area of research is a new development for my supervisor Cornelia de Moor and members of her lab. More students are needed to continue this work and better understand this pathogen, with the end desired outcome of technology for biological control (applications for agriculture). |
| Sectors | Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology |
| Description | Cordycepin and other anti-inflammatory metabolites from fungi |
| Organisation | Kaapa Biotech Oy |
| Country | Finland |
| Sector | Private |
| PI Contribution | I initiated this collaboration on cordycepin other anti-inflammatory compounds from fungi. My laboratory works on identifying the molecular targets of these compounds in both mammalians and insect hosts. The rest of the team has expertise in analytical chemistry (Barrett, Kim) and pharmacokinetics (Gershkovich) from the School of Pharmacy, experts in animal physiology from the School of Biomedical Sciences (Chapman) and mycologists from the School of Biology (Brock, Dyer) in Nottingham and Crop Sciences in Warwick (Chandler). Two Cordyceps growing companies are in the collaboration, GOBA from Slovenia and Kaapa Biotech from Finland. They provide us with Cordyceps samples and strains. A research grant application and a PhD studentship application to Arthritis Research UK application were successful. We are planning to apply to the BBSRC with a focus on the effect of these compounds in insects, once the relevant paper has been published. Three publications have so far resulted from this collaboration and another one is in the manuscript stage. |
| Collaborator Contribution | Prof. Barrett and I have a joint PhD student that has developed a sensitive LC MS/MS method for detecting cordycepin, which enables us to do pharmacokinetics with Dr. Gershkovich. In collaboration with Dr. Kim we are doing metabolomics, trying to identify further compounds. Prof Chapman has trialled cordycepin in a rat model of arthritis. Dr. Chandler and Dr. Dyer help us select candidate fungi based on their biology and culture them. |
| Impact | This is a multidisciplinary collaboration encompassing molecular biology, analytical biochemistry, pharmacokinetics, physiology, mycology. So far 4 publications have resulted: Lee, J.B., Radhi, M., Cipolla, E., Gandhi, R.D., Sarmad, S., Zgair, A., Kim, T.H., Feng, W., Qin, C., Adrower, C., Ortori, C.A., Barrett, D.A., Kagan, L., Fisher, P.M., De Moor, C.H., Gershkovich, P. (2019) A novel nucleoside rescue metabolic pathway may be responsible for the therapeutic effect of orally administered cordycepin. Sci. Rep., 9, 15760. doi: 10.1038/s41598-019-52254-x https://www.nature.com/articles/s41598-019-52254-x.pdf Wellham, P.A.D., Kim, D.-H., Brock, M. and De Moor, C.H. (2019) Coupled biosynthesis of cordycepin and pentostatin in Cordyceps militaris: implications for fungal biology and medicinal natural products. Ann. Transl. Med., 7(Suppl 3), S85. doi: 0.21037/atm.2019.04.25 http://dx.doi.org/10.21037/atm.2019.04.25 Meijer, H.A., Schmidt, T., Gillen S.L., Langlais, C., Jukes-Jones, R., De Moor, C.H., Cain, K., Wilczynska, A. and Martin Bushell (2019). DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity. Nucl. Acids Res., 47, 8224-8238. doi: 10.1093/nar/gkz509 https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz509/5513320?searchresult=1 Ashraf, S., Radhi, M., Gowler, P., Burston, J.J., Gandhi, R.D., Thorn, G.J., Piccinini A.M., Walsh, D.A., Chapman, V. and De Moor, C.H. (2019) The polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritis. Sci. Rep., 9, 4696. doi: 10.1038/s41598-019-41140-1 https://www.nature.com/articles/s41598-019-41140-1 Lee, J.B., Adrower, C., Qin, C., Fischer, P.M., De Moor, C.H. and Gershkovich, P. (2017) Development of cordycepin formulations for preclinical and clinical studies. AAPS PharmSciTech 18, 3219-3226. doi: 10.1208/s12249-017-0795-0 http://eprints.nottingham.ac.uk/42896/ |
| Start Year | 2010 |
| Description | Cordycepin and other anti-inflammatory metabolites from fungi |
| Organisation | Mycomedica |
| Country | Slovenia |
| Sector | Private |
| PI Contribution | I initiated this collaboration on cordycepin other anti-inflammatory compounds from fungi. My laboratory works on identifying the molecular targets of these compounds in both mammalians and insect hosts. The rest of the team has expertise in analytical chemistry (Barrett, Kim) and pharmacokinetics (Gershkovich) from the School of Pharmacy, experts in animal physiology from the School of Biomedical Sciences (Chapman) and mycologists from the School of Biology (Brock, Dyer) in Nottingham and Crop Sciences in Warwick (Chandler). Two Cordyceps growing companies are in the collaboration, GOBA from Slovenia and Kaapa Biotech from Finland. They provide us with Cordyceps samples and strains. A research grant application and a PhD studentship application to Arthritis Research UK application were successful. We are planning to apply to the BBSRC with a focus on the effect of these compounds in insects, once the relevant paper has been published. Three publications have so far resulted from this collaboration and another one is in the manuscript stage. |
| Collaborator Contribution | Prof. Barrett and I have a joint PhD student that has developed a sensitive LC MS/MS method for detecting cordycepin, which enables us to do pharmacokinetics with Dr. Gershkovich. In collaboration with Dr. Kim we are doing metabolomics, trying to identify further compounds. Prof Chapman has trialled cordycepin in a rat model of arthritis. Dr. Chandler and Dr. Dyer help us select candidate fungi based on their biology and culture them. |
| Impact | This is a multidisciplinary collaboration encompassing molecular biology, analytical biochemistry, pharmacokinetics, physiology, mycology. So far 4 publications have resulted: Lee, J.B., Radhi, M., Cipolla, E., Gandhi, R.D., Sarmad, S., Zgair, A., Kim, T.H., Feng, W., Qin, C., Adrower, C., Ortori, C.A., Barrett, D.A., Kagan, L., Fisher, P.M., De Moor, C.H., Gershkovich, P. (2019) A novel nucleoside rescue metabolic pathway may be responsible for the therapeutic effect of orally administered cordycepin. Sci. Rep., 9, 15760. doi: 10.1038/s41598-019-52254-x https://www.nature.com/articles/s41598-019-52254-x.pdf Wellham, P.A.D., Kim, D.-H., Brock, M. and De Moor, C.H. (2019) Coupled biosynthesis of cordycepin and pentostatin in Cordyceps militaris: implications for fungal biology and medicinal natural products. Ann. Transl. Med., 7(Suppl 3), S85. doi: 0.21037/atm.2019.04.25 http://dx.doi.org/10.21037/atm.2019.04.25 Meijer, H.A., Schmidt, T., Gillen S.L., Langlais, C., Jukes-Jones, R., De Moor, C.H., Cain, K., Wilczynska, A. and Martin Bushell (2019). DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity. Nucl. Acids Res., 47, 8224-8238. doi: 10.1093/nar/gkz509 https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz509/5513320?searchresult=1 Ashraf, S., Radhi, M., Gowler, P., Burston, J.J., Gandhi, R.D., Thorn, G.J., Piccinini A.M., Walsh, D.A., Chapman, V. and De Moor, C.H. (2019) The polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritis. Sci. Rep., 9, 4696. doi: 10.1038/s41598-019-41140-1 https://www.nature.com/articles/s41598-019-41140-1 Lee, J.B., Adrower, C., Qin, C., Fischer, P.M., De Moor, C.H. and Gershkovich, P. (2017) Development of cordycepin formulations for preclinical and clinical studies. AAPS PharmSciTech 18, 3219-3226. doi: 10.1208/s12249-017-0795-0 http://eprints.nottingham.ac.uk/42896/ |
| Start Year | 2010 |
| Description | Cordycepin and other anti-inflammatory metabolites from fungi |
| Organisation | University of Nottingham |
| Department | School of Biology Nottingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I initiated this collaboration on cordycepin other anti-inflammatory compounds from fungi. My laboratory works on identifying the molecular targets of these compounds in both mammalians and insect hosts. The rest of the team has expertise in analytical chemistry (Barrett, Kim) and pharmacokinetics (Gershkovich) from the School of Pharmacy, experts in animal physiology from the School of Biomedical Sciences (Chapman) and mycologists from the School of Biology (Brock, Dyer) in Nottingham and Crop Sciences in Warwick (Chandler). Two Cordyceps growing companies are in the collaboration, GOBA from Slovenia and Kaapa Biotech from Finland. They provide us with Cordyceps samples and strains. A research grant application and a PhD studentship application to Arthritis Research UK application were successful. We are planning to apply to the BBSRC with a focus on the effect of these compounds in insects, once the relevant paper has been published. Three publications have so far resulted from this collaboration and another one is in the manuscript stage. |
| Collaborator Contribution | Prof. Barrett and I have a joint PhD student that has developed a sensitive LC MS/MS method for detecting cordycepin, which enables us to do pharmacokinetics with Dr. Gershkovich. In collaboration with Dr. Kim we are doing metabolomics, trying to identify further compounds. Prof Chapman has trialled cordycepin in a rat model of arthritis. Dr. Chandler and Dr. Dyer help us select candidate fungi based on their biology and culture them. |
| Impact | This is a multidisciplinary collaboration encompassing molecular biology, analytical biochemistry, pharmacokinetics, physiology, mycology. So far 4 publications have resulted: Lee, J.B., Radhi, M., Cipolla, E., Gandhi, R.D., Sarmad, S., Zgair, A., Kim, T.H., Feng, W., Qin, C., Adrower, C., Ortori, C.A., Barrett, D.A., Kagan, L., Fisher, P.M., De Moor, C.H., Gershkovich, P. (2019) A novel nucleoside rescue metabolic pathway may be responsible for the therapeutic effect of orally administered cordycepin. Sci. Rep., 9, 15760. doi: 10.1038/s41598-019-52254-x https://www.nature.com/articles/s41598-019-52254-x.pdf Wellham, P.A.D., Kim, D.-H., Brock, M. and De Moor, C.H. (2019) Coupled biosynthesis of cordycepin and pentostatin in Cordyceps militaris: implications for fungal biology and medicinal natural products. Ann. Transl. Med., 7(Suppl 3), S85. doi: 0.21037/atm.2019.04.25 http://dx.doi.org/10.21037/atm.2019.04.25 Meijer, H.A., Schmidt, T., Gillen S.L., Langlais, C., Jukes-Jones, R., De Moor, C.H., Cain, K., Wilczynska, A. and Martin Bushell (2019). DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity. Nucl. Acids Res., 47, 8224-8238. doi: 10.1093/nar/gkz509 https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz509/5513320?searchresult=1 Ashraf, S., Radhi, M., Gowler, P., Burston, J.J., Gandhi, R.D., Thorn, G.J., Piccinini A.M., Walsh, D.A., Chapman, V. and De Moor, C.H. (2019) The polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritis. Sci. Rep., 9, 4696. doi: 10.1038/s41598-019-41140-1 https://www.nature.com/articles/s41598-019-41140-1 Lee, J.B., Adrower, C., Qin, C., Fischer, P.M., De Moor, C.H. and Gershkovich, P. (2017) Development of cordycepin formulations for preclinical and clinical studies. AAPS PharmSciTech 18, 3219-3226. doi: 10.1208/s12249-017-0795-0 http://eprints.nottingham.ac.uk/42896/ |
| Start Year | 2010 |
| Description | Cordycepin and other anti-inflammatory metabolites from fungi |
| Organisation | University of Nottingham |
| Department | School of Biomedical Sciences Nottingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I initiated this collaboration on cordycepin other anti-inflammatory compounds from fungi. My laboratory works on identifying the molecular targets of these compounds in both mammalians and insect hosts. The rest of the team has expertise in analytical chemistry (Barrett, Kim) and pharmacokinetics (Gershkovich) from the School of Pharmacy, experts in animal physiology from the School of Biomedical Sciences (Chapman) and mycologists from the School of Biology (Brock, Dyer) in Nottingham and Crop Sciences in Warwick (Chandler). Two Cordyceps growing companies are in the collaboration, GOBA from Slovenia and Kaapa Biotech from Finland. They provide us with Cordyceps samples and strains. A research grant application and a PhD studentship application to Arthritis Research UK application were successful. We are planning to apply to the BBSRC with a focus on the effect of these compounds in insects, once the relevant paper has been published. Three publications have so far resulted from this collaboration and another one is in the manuscript stage. |
| Collaborator Contribution | Prof. Barrett and I have a joint PhD student that has developed a sensitive LC MS/MS method for detecting cordycepin, which enables us to do pharmacokinetics with Dr. Gershkovich. In collaboration with Dr. Kim we are doing metabolomics, trying to identify further compounds. Prof Chapman has trialled cordycepin in a rat model of arthritis. Dr. Chandler and Dr. Dyer help us select candidate fungi based on their biology and culture them. |
| Impact | This is a multidisciplinary collaboration encompassing molecular biology, analytical biochemistry, pharmacokinetics, physiology, mycology. So far 4 publications have resulted: Lee, J.B., Radhi, M., Cipolla, E., Gandhi, R.D., Sarmad, S., Zgair, A., Kim, T.H., Feng, W., Qin, C., Adrower, C., Ortori, C.A., Barrett, D.A., Kagan, L., Fisher, P.M., De Moor, C.H., Gershkovich, P. (2019) A novel nucleoside rescue metabolic pathway may be responsible for the therapeutic effect of orally administered cordycepin. Sci. Rep., 9, 15760. doi: 10.1038/s41598-019-52254-x https://www.nature.com/articles/s41598-019-52254-x.pdf Wellham, P.A.D., Kim, D.-H., Brock, M. and De Moor, C.H. (2019) Coupled biosynthesis of cordycepin and pentostatin in Cordyceps militaris: implications for fungal biology and medicinal natural products. Ann. Transl. Med., 7(Suppl 3), S85. doi: 0.21037/atm.2019.04.25 http://dx.doi.org/10.21037/atm.2019.04.25 Meijer, H.A., Schmidt, T., Gillen S.L., Langlais, C., Jukes-Jones, R., De Moor, C.H., Cain, K., Wilczynska, A. and Martin Bushell (2019). DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity. Nucl. Acids Res., 47, 8224-8238. doi: 10.1093/nar/gkz509 https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz509/5513320?searchresult=1 Ashraf, S., Radhi, M., Gowler, P., Burston, J.J., Gandhi, R.D., Thorn, G.J., Piccinini A.M., Walsh, D.A., Chapman, V. and De Moor, C.H. (2019) The polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritis. Sci. Rep., 9, 4696. doi: 10.1038/s41598-019-41140-1 https://www.nature.com/articles/s41598-019-41140-1 Lee, J.B., Adrower, C., Qin, C., Fischer, P.M., De Moor, C.H. and Gershkovich, P. (2017) Development of cordycepin formulations for preclinical and clinical studies. AAPS PharmSciTech 18, 3219-3226. doi: 10.1208/s12249-017-0795-0 http://eprints.nottingham.ac.uk/42896/ |
| Start Year | 2010 |
| Description | Cordycepin and other anti-inflammatory metabolites from fungi |
| Organisation | University of Nottingham |
| Department | School of Pharmacy |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I initiated this collaboration on cordycepin other anti-inflammatory compounds from fungi. My laboratory works on identifying the molecular targets of these compounds in both mammalians and insect hosts. The rest of the team has expertise in analytical chemistry (Barrett, Kim) and pharmacokinetics (Gershkovich) from the School of Pharmacy, experts in animal physiology from the School of Biomedical Sciences (Chapman) and mycologists from the School of Biology (Brock, Dyer) in Nottingham and Crop Sciences in Warwick (Chandler). Two Cordyceps growing companies are in the collaboration, GOBA from Slovenia and Kaapa Biotech from Finland. They provide us with Cordyceps samples and strains. A research grant application and a PhD studentship application to Arthritis Research UK application were successful. We are planning to apply to the BBSRC with a focus on the effect of these compounds in insects, once the relevant paper has been published. Three publications have so far resulted from this collaboration and another one is in the manuscript stage. |
| Collaborator Contribution | Prof. Barrett and I have a joint PhD student that has developed a sensitive LC MS/MS method for detecting cordycepin, which enables us to do pharmacokinetics with Dr. Gershkovich. In collaboration with Dr. Kim we are doing metabolomics, trying to identify further compounds. Prof Chapman has trialled cordycepin in a rat model of arthritis. Dr. Chandler and Dr. Dyer help us select candidate fungi based on their biology and culture them. |
| Impact | This is a multidisciplinary collaboration encompassing molecular biology, analytical biochemistry, pharmacokinetics, physiology, mycology. So far 4 publications have resulted: Lee, J.B., Radhi, M., Cipolla, E., Gandhi, R.D., Sarmad, S., Zgair, A., Kim, T.H., Feng, W., Qin, C., Adrower, C., Ortori, C.A., Barrett, D.A., Kagan, L., Fisher, P.M., De Moor, C.H., Gershkovich, P. (2019) A novel nucleoside rescue metabolic pathway may be responsible for the therapeutic effect of orally administered cordycepin. Sci. Rep., 9, 15760. doi: 10.1038/s41598-019-52254-x https://www.nature.com/articles/s41598-019-52254-x.pdf Wellham, P.A.D., Kim, D.-H., Brock, M. and De Moor, C.H. (2019) Coupled biosynthesis of cordycepin and pentostatin in Cordyceps militaris: implications for fungal biology and medicinal natural products. Ann. Transl. Med., 7(Suppl 3), S85. doi: 0.21037/atm.2019.04.25 http://dx.doi.org/10.21037/atm.2019.04.25 Meijer, H.A., Schmidt, T., Gillen S.L., Langlais, C., Jukes-Jones, R., De Moor, C.H., Cain, K., Wilczynska, A. and Martin Bushell (2019). DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity. Nucl. Acids Res., 47, 8224-8238. doi: 10.1093/nar/gkz509 https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz509/5513320?searchresult=1 Ashraf, S., Radhi, M., Gowler, P., Burston, J.J., Gandhi, R.D., Thorn, G.J., Piccinini A.M., Walsh, D.A., Chapman, V. and De Moor, C.H. (2019) The polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritis. Sci. Rep., 9, 4696. doi: 10.1038/s41598-019-41140-1 https://www.nature.com/articles/s41598-019-41140-1 Lee, J.B., Adrower, C., Qin, C., Fischer, P.M., De Moor, C.H. and Gershkovich, P. (2017) Development of cordycepin formulations for preclinical and clinical studies. AAPS PharmSciTech 18, 3219-3226. doi: 10.1208/s12249-017-0795-0 http://eprints.nottingham.ac.uk/42896/ |
| Start Year | 2010 |
| Description | Cordycepin and other anti-inflammatory metabolites from fungi |
| Organisation | University of Warwick |
| Department | Warwick Crop Centre |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I initiated this collaboration on cordycepin other anti-inflammatory compounds from fungi. My laboratory works on identifying the molecular targets of these compounds in both mammalians and insect hosts. The rest of the team has expertise in analytical chemistry (Barrett, Kim) and pharmacokinetics (Gershkovich) from the School of Pharmacy, experts in animal physiology from the School of Biomedical Sciences (Chapman) and mycologists from the School of Biology (Brock, Dyer) in Nottingham and Crop Sciences in Warwick (Chandler). Two Cordyceps growing companies are in the collaboration, GOBA from Slovenia and Kaapa Biotech from Finland. They provide us with Cordyceps samples and strains. A research grant application and a PhD studentship application to Arthritis Research UK application were successful. We are planning to apply to the BBSRC with a focus on the effect of these compounds in insects, once the relevant paper has been published. Three publications have so far resulted from this collaboration and another one is in the manuscript stage. |
| Collaborator Contribution | Prof. Barrett and I have a joint PhD student that has developed a sensitive LC MS/MS method for detecting cordycepin, which enables us to do pharmacokinetics with Dr. Gershkovich. In collaboration with Dr. Kim we are doing metabolomics, trying to identify further compounds. Prof Chapman has trialled cordycepin in a rat model of arthritis. Dr. Chandler and Dr. Dyer help us select candidate fungi based on their biology and culture them. |
| Impact | This is a multidisciplinary collaboration encompassing molecular biology, analytical biochemistry, pharmacokinetics, physiology, mycology. So far 4 publications have resulted: Lee, J.B., Radhi, M., Cipolla, E., Gandhi, R.D., Sarmad, S., Zgair, A., Kim, T.H., Feng, W., Qin, C., Adrower, C., Ortori, C.A., Barrett, D.A., Kagan, L., Fisher, P.M., De Moor, C.H., Gershkovich, P. (2019) A novel nucleoside rescue metabolic pathway may be responsible for the therapeutic effect of orally administered cordycepin. Sci. Rep., 9, 15760. doi: 10.1038/s41598-019-52254-x https://www.nature.com/articles/s41598-019-52254-x.pdf Wellham, P.A.D., Kim, D.-H., Brock, M. and De Moor, C.H. (2019) Coupled biosynthesis of cordycepin and pentostatin in Cordyceps militaris: implications for fungal biology and medicinal natural products. Ann. Transl. Med., 7(Suppl 3), S85. doi: 0.21037/atm.2019.04.25 http://dx.doi.org/10.21037/atm.2019.04.25 Meijer, H.A., Schmidt, T., Gillen S.L., Langlais, C., Jukes-Jones, R., De Moor, C.H., Cain, K., Wilczynska, A. and Martin Bushell (2019). DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity. Nucl. Acids Res., 47, 8224-8238. doi: 10.1093/nar/gkz509 https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz509/5513320?searchresult=1 Ashraf, S., Radhi, M., Gowler, P., Burston, J.J., Gandhi, R.D., Thorn, G.J., Piccinini A.M., Walsh, D.A., Chapman, V. and De Moor, C.H. (2019) The polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritis. Sci. Rep., 9, 4696. doi: 10.1038/s41598-019-41140-1 https://www.nature.com/articles/s41598-019-41140-1 Lee, J.B., Adrower, C., Qin, C., Fischer, P.M., De Moor, C.H. and Gershkovich, P. (2017) Development of cordycepin formulations for preclinical and clinical studies. AAPS PharmSciTech 18, 3219-3226. doi: 10.1208/s12249-017-0795-0 http://eprints.nottingham.ac.uk/42896/ |
| Start Year | 2010 |
| Description | Pint of Science Festival 2018. "Planet Earth" event. |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | I was involved in the organisation and presentation of the "Planet Earth" stream - a three-night event of talks to the public with expert speakers. As well as talks, there were demonstrations of simple science "experiments". |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.nottingham.ac.uk/home/featureevents/2018/pint-of-science-festival-2018.aspx |