Amgen Scholars: Announcements of Opportunity

Below are Announcements of Opportunity posted by Caltech faculty for the Amgen Scholars program.

Announcements of Opportunity are posted as they are received. Please check back regularly for new AO submissions! Remember: This is just one way that you can go about identifying a suitable project and/or mentor. For additional tips on identifying a mentor click here.

Please remember:

Students pursuing Amgen must be U.S. citizens, U.S. permanent residents, or students with DACA status.
Students pursuing Amgen must complete the 10-week program from June 21 - August 25, 2023. Students must commit to these dates. No exceptions will be made.
Accepted students must live in provided Caltech housing.

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Project:

Deciphering dark proteome-mediated transcriptional control at single-molecule resolution

Disciplines:

Biology, Biophysics, Chemistry, Biochemistry

Mentor:

Shasha Chong, Assistant Professor of Chemistry, (CCE), schong@caltech.edu, Phone: 626-395-5736

Mentor URL:

https://www.schonglab.com (opens in new window)

Background:

Intrinsically disordered protein regions (IDRs) are ubiquitous in eukaryotic proteomes, e.g., they constitute nearly 50% of the human proteome. They are referred to as the “dark proteome” and perform functions in numerous essential cellular processes with unclear mechanisms. Further putting a spotlight on IDRs are many recent discoveries on functionally relevant liquid-liquid phase separation in the cell, which is often driven by IDR-mediated biomolecular interactions. Our lab investigate the IDRs involved in transcriptional regulation and aim to ultimately reach a predictive understanding of sequence-interaction-function relationships of the entire dark proteome. Our research will also shed new light on the molecular mechanisms of different cancers and suggest new therapeutic strategies.

Complex biomolecular transactions, such as those involved in transcriptional regulation, are often highly dynamic, reversible, and heterogeneous. An in-depth mechanistic understanding of these transactions often requires visualizing biomolecules one at a time with high spatiotemporal resolution. To this end, we develop novel single-molecule imaging methods and combine them with genome editing, biochemical, genomic, proteomic, and bioinformatic approaches in our research.

Description:

The student will participate in one or more experiments that investigate the interaction behaviors and transcriptional regulation functions of specific IDRs in live mammalian cells. Typical experiments include generating plasmids for protein expression in cells, engineering cell lines, and quantitative fluorescence imaging of proteins/nucleic acids in cells.

References:

1. Chong, S.; Dugast-Darzacq, C.; Liu, Z.; Dong, P.; Dailey, G. M.; Cattoglio, C.; Heckert, A.; Banala, S.; Lavis, L.; Darzacq, X.; Tjian, R. (2018) “Imaging Dynamic and Selective Low-Complexity Domain Interactions That Control Gene Transcription” Science, 361, eaar2555.

2. Chong, S.; Graham, T. G. W.; Dugast-Darzacq, C.; Dailey, G. M.; Darzacq, X.; Tjian, R. (2022) "Tuning levels of low-complexity domain interactions to modulate endogenous oncogenic transcription" Molecular Cell, 82, 2084-2097.

3. Chong, S.†; Mir, M. (2021) "Towards decoding the sequence-based grammar governing the functions of intrinsically disordered protein regions" Journal of Molecular Biology, 433, 166724. †Corresponding author

4. Irgen-Gioro, S.*; Yoshida, S. R.*; Walling, V.; Chong, S.† (2022) "Fixation can change the appearance of phase separation in living cells" BioRxiv, 2022.05.06.490956; doi: https://doi.org/10.1101/2022.05.06.490956. †Corresponding author. *Equal contribution

Student Requirements:

Having one or more than one of the following skills will be helpful: molecular cloning, mammalian tissue culture, fluorescence microscopy, and computer programming

Programs:

This AO can be done under the following programs:

		Program	Available To
		Amgen Scholars	Non-Caltech students only
		SURF	both Caltech and non-Caltech students

Click on a program name for program info and application requirements.

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