Project/Area Number |
19K16273
|
Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 46010:Neuroscience-general-related
|
Research Institution | Institute of Physical and Chemical Research |
Principal Investigator |
Krzyzanowski Marek 国立研究開発法人理化学研究所, 脳神経科学研究センター, 基礎科学特別研究員 (10837181)
|
Project Period (FY) |
2019-04-01 – 2023-03-31
|
Project Status |
Discontinued (Fiscal Year 2022)
|
Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
|
Keywords | mRNA translation / ribosome / neuron / psychiatric diseases / RNA granules / translation / psychiatric disorders / memory / autism / brain / RNA |
Outline of Research at the Start |
RNA granules deliver mRNAs to the distant parts of neuronal cells, such as axon and dendrites. I will study how RNA granules change in response to neuronal activity and in mouse-models of neuropsychiatric disorders to investigate their role in such brain functions as memory and emotions.
|
Outline of Annual Research Achievements |
Proteins implicated in translation initiation were identified at the beginning of this project as enriched in neuronal RNA granules. During the last year of the project I focused on studying translation initiation in mutant mice with behavioral abnormalities resembling human neuropsychiatric disorders, hypothesizing that de-regulated translation initiation contributes to aberrant behavior of these mice. To this end I developed a method to purify the pre-initiation complexes from brain tissue by immunoprecipitation. Western blotting confirmed the presence of known initiation factors and 40S ribosomal proteins as well as apparent absence of 60S ribosomal proteins. This suggested the presence of relatively enriched pre-initiation complexes in the immunoprecipitates. Next, protein composition of the purified pre-initiation complexes from wild type and mutant mice was compared by relative quantification mass spectrometry. Preliminary results confirmed strong enrichment of translation initiation factors and 40S ribosomal proteins in purified complexes and revealed enrichment of a few proteins in the complexes from mutant mice. Identified proteins could be potential candidates for a future follow-up study.
|