Signal transduction within crowded cellular compartments is essential for the physiological function of cells. Although the accuracy with which receptors can probe the concentration of ligands has been thoroughly investigated in dilute systems, the …
We are deciphering the control mechanism of the unfolded protein response and protein homeostasis to open new therapeutic avenues for age-associated and protein folding diseases
The study of macromolecular crowding is indispensable for understanding cellular physiology and biochemistry. We are investigating how crowding affects quantitatively the cellular biochemistry, and qualitatively cellular physiology.
The unfolded protein response (UPR) is a collection of cellular feedback mechanisms that seek to maintain protein folding homeostasis in the endoplasmic reticulum (ER). When the ER is ‘stressed’, either through high protein folding demand or …
Stress detection in the endoplasmic reticulum is essential for protein homeostasis. Here, a mathematical model of the unfolded protein response is used to demonstrate the advantage of a stress-sensing mechanism based on BiP dissociation from Ire1, as opposed to direct unfolded protein–Ire1 interaction, to activate the response.
Cellular condensates-phase-separated concentrates of proteins and nucleic acids-provide organizational structure for biochemistry that is distinct from membrane-bound compartments. It has been suggested that one major function of cellular condensates …
The origin of cellular compartmentalization has long been viewed as paralleling the origin of life. Historically, membrane-bound organelles have been presented as the canonical examples of compartmentalization. However, recent interest in cellular …
In type I diabetes, an autoimmune disease mediated by autoreactive T-cells that attack insulin-secreting pancreatic beta-cells, it has been suggested that disease progression may additionally require protective mechanisms in the target tissue to …
The physicochemical properties of cellular environments with a high macromolecular content have been systematically characterized to explain differences observed in the diffusion coefficients, kinetics parameters, and thermodynamic properties of …