Hur fungerar reglering av icke-specifika membranproteiner?

Many molecular programs in our body execute differently from binary on/off sensing (i.e. being dependent solely on the presence or absence of a single factor) but instead rely on interplay of many proteins, patterns of the ligands and even the size of what is bound to the cell surface.

We have discovered that the Notch receptor is more sensitive to activation with a larger ligand construct than a smaller one.

Similar results have been seen in B-cell receptor (BCR) activation, that the footprint of what is bound is important, not only the specificity of the receptor.

We hypothesize that one reason for this could be that the receptor should initiate activation only upon binding other cells (in the case of Notch) or if the antigen is large enough (in the case of BCRs), i.e. that there is a logic gate applied to the receptor: binding AND footprint/pattern is required.

How these mechanisms could arise molecularly is less clear and here we propose a research program that will elucidate these questions.

Error free function of these basal mechanisms is undoubtedly important, it is easy to see how non-specificity could drive disease, immune disorders and neurodegeneration in these particular examples.

Using novel methods developed in my lab base on protein-decorated nanostructures made out of DNA we are uniquely positioned to investigate these effects and at the same time contribute key innovations that will benefit both basic research and technologies for new therapeutics.