INTEGRATIVE MULTI-SCALE SYSTEMS ANALYSIS OF GENE-EXPRESSION-DRIVEN AGING MORBIDITY - PROJECT SUMMARY IN A W…

Assistance award details

Assistance award identifier

ASST_NON_R00AG068544_075

FAIN

R00AG068544

Recipient

NORTHWESTERN UNIVERSITY

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$720,082

Period

Sep 15, 2020 – Dec 31, 2026

Fiscal year

2024

Place of performance state

IL

Source file

FY2024_All_Assistance_Full_20261006.zip

Description

INTEGRATIVE MULTI-SCALE SYSTEMS ANALYSIS OF GENE-EXPRESSION-DRIVEN AGING MORBIDITY - PROJECT SUMMARY IN A WELL-RECEIVED PREPRINT, THE INVESTIGATOR IDENTIFIED THROUGH UNBIASED ANALYSIS OF OWN AND PUBLISHED DATASETS THAT DURING AGING, AND INFECTION OF THE LUNG WITH INFLUENZA A, THERE IS A PROGRESSIVE IMBALANCE IN THE TRANSCRIPT LEVELS ENCODED BY SHORT GENES RELATIVE TO THOSE ENCODED BY LONG GENES. FAILURE OF GENE EXPRESSION HOMEOSTASIS IMPACTS THE RHEOSTATIC ABILITY OF ALMOST ALL CELLULAR PROCESSES IMPLICATED IN AGING IMPAIRING ORGAN FUNCTION, PARTICULARLY IN RESPONSE TO SYSTEMIC STRESS. TRANSCRIPTOME IMBALANCE COULD ACCOUNT FOR MANIFESTATIONS OF AGING THROUGH SEVERAL POTENTIAL MECHANISMS, INCLUDING: 1) THE DYSREGULATION OF INDIVIDUAL GENES, 2) A DYSREGULATION OF THE STOICHIOMETRY OF MACROMOLECULAR COMPLEXES, 3) A RELATIVE UPREGULATION OF SHORT EARLY-RESPONSE INFLAMMATORY GENES, 4) A BREAKDOWN OF THE COORDINATION BETWEEN MOLECULAR PATHWAYS AND PROCESSES ENCODED BY GENES OF DIFFERENT LENGTHS AND 5) A REDUCTION IN THE CAPACITY OF PROTEIN HOMEOSTASIS AND CELL STRESS RESPONSES TO RESPOND TOWARDS EXTERNAL STIMULI BY SEQUESTERING ITS ACTIVITY TOWARD A BUFFERING OF TRANSCRIPTOME IMBALANCE. THE INVESTIGATOR WILL TEST THE HYPOTHESIS THAT DURING AGING TRANSCRIPTOME IMBALANCE GLOBALLY INTERFERES WITH THE FUNCTIONS ENCODED BY THE GENOME AND CONTRIBUTES TO THE LOSS OF RESILIENCE IN OLDER INDIVIDUALS. TO ADDRESS THIS FUNDAMENTAL QUESTION, HE WILL FOCUS ON INNOVATIVE MAMMALIAN EX VIVO, IN VITRO, AND IN VIVO MODELS OF AGE-DEPENDENT TRANSCRIPTOME IMBALANCE, AND MACHINE-LEARNING APPROACHES. REFLECTING THE INTERDISCIPLINARY CHARACTER, HE WILL WORK UNDER THE SUPERVISION OF HIS MAIN MENTOR DR. AMARAL, A NETWORK SCIENTIST AND DATA- SCIENTIST, AND HIS CO-MENTOR DR. MORIMOTO, A MOLECULAR BIOLOGIST STUDYING PROTEIN HOMEOSTASIS AND AGING. FURTHER MARKING HIS TRANSITION TO INDEPENDENCE, HE WILL BE MENTORED BY DR. BUDINGER, AN IMMUNOLOGIST STUDYING CHANGES IN IMMUNE AGING, AND DR. MCNALLY, A GEN