Research on the Role of Post-Translational Modifications in Human Health and Disease

Post Date: June 26, 2026

Expiration Date: June 26, 2028

Purpose

This topic encourages research to examine the mechanistic roles of understudied post-translation modifications (PTMs) and PTM crosstalk in the biology of human health and disease, such as cancer.

Background

PTMs are crucial to biological processes, enabling cells to respond and adapt to extrinsic and intrinsic stimuli, and perform a central regulatory mechanism in normal cellular function, organismal development, tissue maintenance, and stress response. PTMs exert their various functions by impacting different aspects of protein behavior, including enzymatic activity, stability, interactions with other molecules, and subcellular localization. 

To date, more than 400 different kinds of PTMs have been detected, about one fourth of which have been linked to human diseases. Among these, phosphorylation, acetylation, methylation and ubiquitination account for the largest number of known disease-associated modifications. Others, such as glycosylation, lactylation, serotonylation, sumoylation, myristoylation and succinylation, etc., remain understudied. It remains poorly understood how varied PTMs crosstalk synergistically or antagonistically to influence protein function and localization, and overall cellular state. This knowledge gap raises important questions regarding the true extent of disease-associated PTMs and what other roles and functions of PTMs have been overlooked due to the focus on a narrowly defined set of modifications. Adding to the challenges, current PTM research (including crosstalk) mostly concentrates on a few proteins such as histones, transcription factors (TFs) and signaling molecules. Broadening the repertoire of PTMs and their substrates will enable a broader understanding of their complex interplay and biological significance in human health and disease.

Recent technological breakthroughs in PTM identification and characterization offers an untapped potential to study diverse PTMs, their crosstalk, and coordinated roles in health and disease. These include computational methodologies, mass spectrometry enrichment techniques, adoption of unnatural amino acids and mimetics, bio-orthogonal chemistry, single-cell omics technologies, and utilization of AlphaFold protein structure databases. Furthermore, advancements in targeted protein degradation and the development of chemical inducers of proximity offer pioneering approaches to interrogate disease-relevant protein-PTMs.

This topic encourages applications that promote:

• mechanistic research on novel functions of understudied and lesser known PTMs; PTM substrates besides histones, TFs and signaling molecules; PTM crosstalk; and spatiotemporal dynamics of PTMs in human health and disease
• leveraging and development of advanced technologies for PTM discovery and mechanistic characterization 
• interdisciplinary collaboration between PTM experts, cell biologists, data scientists, computational modelers, chemists, and biophysicists to examine understudied PTMs and their crosstalk