# NIH grant: Uncovering Non-canonical Roles of Phosphagen Systems in Stress Resilience Using C. elegans (1R15GM164975-01) — retained record

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NIH grant 1R15GM164975-01: Uncovering Non-canonical Roles of Phosphagen Systems in Stress Resilience Using C. elegans
Institute: {'code': 'GM', 'abbreviation': 'NIGMS', 'name': 'National Institute of General Medical Sciences', 'admin_org_id': '12500024', 'admin_funding_url': ''}. PI: Sarah Rachel Fausett. Award: $546500.
Start: 2026-08-08T00:00:00.
Abstract
This proposal seeks to understand emerging non-canonical roles of phosphagen kinases in
cellular and organismal stress responses. Phosphagen kinases are a class of enzymes that
include creatine kinases. They are well-known to support energy balance, but other functions
are less well-understood. Recent research suggests that augmenting the activity of these
enzymes may be sufficient to increase cellular stress responses, which are important in
preserving tissue health during aging and disease. This makes phosphagen kinases potentially
exciting targets for aging and disease intervention, but we still don’t fully understand how they
work. Furthermore, their functions may depend on which tissues different versions of the
enzymes are present in and what they are doing in each tissue. Understanding tissue-specific
roles of enzymes is challenging in humans and laboratory models such as rodents and cell
culture. In contrast, the roundworm, C. elegans, is a well-established and efficient model system
that is perfectly suited for addressing these questions, and it shares many genes and biological
processes in common with humans. In this study, we propose to use this model to:
 1) Identify which of three different versions of phosphagen kinases support tolerance to
 diverse stresses
 2) Test the hypothesis that phosphagen kinases protect cells by acting similarly to
 antioxidants and preserving the function of energy machinery. Simultaneously, identify
 which tissues are most affected by phosphagen kinase function and sensitive to its loss
 through tissue-specific genetic manipulations.
 3) Determine whether phosphagen kinase function changes the way other enzymes and
 genes act to support stress response using new genetic sequencing technologies.
Altogether, this work will illuminate mechanisms of phosphagen kinase function under stress.
paving the way for novel aging and disease interventions. Furthermore, through this funding, at
least 9 undergraduate students and 2 graduate students will be trained in state-of-the-art
biomedical science, fostering the next generation of scientists and America’s continued
superiority in biomedical research.
```



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