Restoring immune fitness through biophysical manipulations

While the identification of “cell types” often relies on well-defined surface markers or transcriptional repertoires, characterizing “cell states” proves to be a more nuanced challenge, demanding a multiparametric analysis.

Hence, functionally different cell states are often overlooked in health and diseases yet constitute an immense opportunity for medical exploitation.

The complexity of cell state definition arises from the absence of clearly defined conceptual parameters, along with the necessary methodologies to measure them.Critical to cellular function are the collective biophysical properties, such as stiffness, fluidity, viscosity and electric potential.

Importantly, such collective properties might change without notable changes in transcriptome or proteome dictating the cell fitness.

Therefore, there is a compelling need to comprehensively map these properties in health and disease; exploit them as biomarkers for various cell states; and manipulate them for optimal cell fitness.In this proposal, by developing and applying state-of-the art methodologies, we will answer the following questions.Is there a functional biophysical state heterogeneity within the same immune cell types?Do diseases cause different biophysical cell states, leading to suboptimal immune cell fitness and functionality?What are the underlying molecular codes for biophysical state heterogeneity?Can we manipulate the biophysical properties to restore optimal immune cell function