2019 Fiscal Year Final Research Report
Establishing a framework for EGFR attenuation through structure-guided targeting of GGA2
| Project/Area Number |
19K21288
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| Project/Area Number (Other) |
18H06183 (2018)
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund (2019)
Single-year Grants (2018) |
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| Review Section |
0901:Oncology and related fields
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
Bokhove Marcel 福島県立医科大学, 医学部, 博士研究員 (30825526)
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| Project Period (FY) |
2018-08-24 – 2020-03-31
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| Keywords | GGA2 / EGFR / Crystallography / Signal-disruption / Protein complex / FLIM / Confocal microscopy / Adaptor protein complex |
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| Outline of Final Research Achievements |
The goal is to obtain a GGA2-EGFR-jxt complex to design anticancer drugs. I made many constructs to study the interaction for structural studies. I could not corroborate previous experiments. Therefore,I made fluorescent resonance energy transfer pairs for fluorescence microscopy. Many constructs were screened for interactions, but I was unable to obtain a complex.
A GGA2 monoclonal would be an invaluable tool in detection of GGA2 in tumours of patients with EGFR-dependent cancers. I produced GGA2hinge, which was used to generate monoclonal antibodies. I purified the antibody from culture medium, which is now used to analyse patient materials.
I shifted my project to the mu adaptor protein (APmu) involved in EGFR recycling. Many (un)fused constructs were made for expression in bacterial cells. I was unable to obtain protein for structure studies. Expression in mammalian cells also failed, suggesting that APmu is toxic. More experiments are needed, but that is outside the time limit.
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| Free Research Field |
Structural biology
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| Academic Significance and Societal Importance of the Research Achievements |
I could not achieve my goal. I wanted to develop anticancer drugs to interfere with GGA2-EGFR by structure-based design. No suitable protein complex was made.
I could make protein for GGA2 antibody generation and purification. This antibody could be a tool towards personalised cancer treatment.
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