Mathematical Biology

Molecular Control Mechanisms of the Unfolded Protein Response

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

Mathematical Modeling of Biomedical Systems

We investigate complex biomedical systems comprising many interacting components, where modeling and theory may aid in the identification of the key mechanisms underlying the behavior of the system as a whole.

Information processing by endoplasmic reticulum stress sensors

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 …

How to design an optimal sensor network for the unfolded protein response

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.

Unraveling the contribution of pancreatic beta-cell suicide in autoimmune type 1 diabetes

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 …

Effects of protein quality control machinery on protein homeostasis

In the endoplasmic reticulum, protein production occurs through a complex set of reaction networks which synthesize and fold protein polypeptides. Proteins can misfold due to mutation or cellular stress. Accumulation of misfolded proteins can lead to …

A model of the unfolded protein response: Pancreatic beta-cell as a case study

Pancreatic β-cell failure is increasingly recognized as central to the progression of diabetes mellitus. Different causes are implicated in the onset of β-cell stress, dysfunction or death. Recent genetic and biochemical evidence both in humans and …