In order to do any biochemical studies of the huntingtin protein, I must first purify the protein in large amounts. The current protocol for protein purification is adapted from other published protocols and requires a long incubation of clarified cell lysate with FLAG resin which means my protein is sitting around with proteases and other contaminants for a long period of time.

To potentially improve yields and sample quality, it would perhaps be beneficial to have an additional quick enrichment step, such as a heparin resin purification step prior to FLAG binding. This may have the added benefit of removing contaminating nucleic acid material. To test this hypothesis, I conducted small-scale purification of Q23 HTT-HAP40 samples in different buffer systems using heparin and FLAG affinity chromatography.

It worked! The enrichment was not substantial but the protein binds heparin, albeit weakly so this is definitely an opportunity for further optimisation and investigation of the heparin binding characteristics of huntingtin, which could prove useful in other experiments. Read about the experiment here on Zenodo.