Alex Gillis

We're excited to share this work! Have had a lot of fun trying to tackle this problem & some surprising results along the way.

Pretty happy to share this work on RNA polymerase II! We had a lot of fun studying this seemingly quite fundamental component of the system controlling Pol II levels & transcription. Amazing to get to work closely with Ana's group on this, combining imaging with genomics.

@KLabGPCR @NatureNeuro Yes, I noted that! I ask as there is a fair bit of literature on mixed strain backgrounds altering phenotypes - you might be interested in this classic review on exactly this problem. doi.org/10.1016/s0166-…

@acftbl @NatureNeuro The study is littermate controlled

Our paper is out today @NatureNeuro. We find a new player controlling mu-opioid receptor trafficking via effects on cholesterol: Ptchd1. Mice lacking Ptchd1 do not develop opioid tolerance and their neurons don't desensitize. nature.com/articles/s4159…

@samuel_b_phd Near the bottom and going backwards. All of us working within Aus know that firsthand.

@samuel_b_phd (Germany of course being yet another country investing a far greater % GDP into research than Australia!)

@samuel_b_phd I have to say Sam, BioNTech might disagree about which country that mRNA vaccine was created in…

fascinating and ambitious work. @tobinatthelab Do you have any further data on the apparent selectivity over M2/3? It would be good to see HTL9936 tested in an additional assay to pERK, tested for antagonism, or some competition affinity measurements.

This is only becoming more important as more of us are pushed into casual or precarious employment. Big companies like USYD will exploit you if you let them.

Reminder to join your union wherever ever you work. There’s a lot that is crook about modern unis but pressure from organised labour protects workers. I am one (hopefully of many) beneficiary of this campaign against historical underpayment.

The precise role of MOR phosphorylation, and βarrestin recruitment, in this is an interesting outstanding question. More critically, it is unclear to what extent tolerance and withdrawal signs relate to 'addictive liability' of certain ligands.

As we discuss in our commentary, there is clearly a complex and yet to be understood series of mechanisms leading to both opioid tolerance and somatic withdrawal. doi.org/10.1038/s41386…

With the publication of this interesting paper (and our associated commentary), I thought I would go through some elements of the broader discussion to highlight some work we were unable to cite. nature.com/articles/s4138…