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Ribosome remodeling as a mechanism of translational control during stress

Award Number: R15GM146171
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Ribosome remodeling as a mechanism of translational control during stress - PROJECT SUMMARY Translational control is one of the major gene expression regulation mechanisms in the cell and its dysregulation leads to many human diseases. Ribosomes in general are viewed as constitutive molecular machines where protein synthesis takes place, however, this view has been recently challenged supporting the hypothesis of ribosome specialization and opening completely new field of research. This project will investigate the fundamental concept of ribosome specialization in protozoa using Leishmania as a model organism. In contrast to other eukaryotes, trypanosomatids including Leishmania species are unicellular organisms and their control of gene expression is mostly achieved during mRNA translation. Therefore, this protozoan represents an excellent model organism to study the role of ribosome specialization in mRNA translation regulation. Environment including temperature, pH, nutrition conditions plays a big role in gene expression regulation, however, it is poorly understood what molecular players are involved in the regulation of translation during environmental stresses and change of host. It is known that translation is globally repressed during the heat shock, however, some mRNAs escape translational repression and their translation is enhanced. Translation of mRNAs encoding for proteins involved in stress response is very important for the Leishmania ability to cope with stress, its differentiation and survival, however, it is not well understood how heat-induced mRNAs escape the global translational repression during the heat stress. This project is based on the hypothesis that ribosome composition undergoes a substantial change during heat stress to promote efficient translation of subset of mRNAs encoding for proteins involved in stress response. The proposed study will provide new information at several different levels: (Aim 1) it will identify on genome-wide scale subset of mRNAs that are actively translated during the heat stress; (Aim 2) it will reveal changes in ribosome composition of Leishmania during the heat stress; and finally, (Aim 3) it will examine using CRISPR/Cas9 knock-out screen what proteins indeed promote selective translation of heat-induced transcripts and what role they play in the life cycle of Leishmania. This comprehensive multidisciplinary approach will reveal for the first time how transcripts selectively rely on specific ribosome components/regulators for their efficient translation during stress in protozoa and establish their role in Leishmania differentiation.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$5 )
2025	2022	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Biomedical Research and Research Training	000	1	9/11/2025	NEW	-$5
														Subtotal = -$5

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Biomedical Research and Research Training	001	1	10/27/2023	SUPPLEMENT FOR EXPANSION	$0
2024	2022	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Biomedical Research and Research Training	000	1	10/27/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $99,658 )
2023	2023	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Biomedical Research and Research Training	000	1	5/22/2023	SUPPLEMENT FOR EXPANSION	$99,658
														Subtotal = $99,658

Issue Date FY: 2022 ( Subtotal = $459,000 )
2022	2022	TEXAS TECH UNIVERSITY SYSTEM	2500 BROADWAY	LUBBOCK	TX	79409	LUBBOCK	USA	Biomedical Research and Research Training	000	1	4/11/2022	NEW	$459,000
														Subtotal = $459,000

Grand Total All Awards = $558,653

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Ribosome remodeling as a mechanism of translational control during stress

Award Number: R15GM146171

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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