John O’Neill

Reconstitution of the human cellular circadian clock
Group Leader page

Circadian rhythms are driven by endogenous clocks within every cell, that time almost every aspect of our biology to a 24h beat. When this daily timekeeping is disrupted, through aging or shift-work for example, we see a greatly increased risk of chronic diseases such as T2 diabetes and Alzheimer’s, as well as some cancers.

To understand why, the O’Neill group is trying to understand the fundamental mechanisms of the biological clockwork within human cells. In most circumstances, cellular circadian rhythms seem to be intimately linked with daily cycles of transcriptional activation and repression. There are several examples where this is not the case, however, in red blood cells for example. Most importantly, the enzymatic mechanisms that together act post-translationally to determine the ~24h period of our circadian rhythm are not well understood.

In order to try and get a better grip on the essential molecular mechanisms of the cellular clock, you will use genome editing to knock out all of the core clock genes from human cells. You will then reintroduce them under inducible gene expression systems. This will allow the essential determinants of daily biological timekeeping to be interrogated in exquisite detail for the first time.

The successful applicant would hold, or be due to complete, a degree in biochemistry, cell biology or a related area. You should be enthusiastic, creative, and have good communication, organisational and numeracy skills. Scientific computing skills would also be advantageous. Prior lab experience desirable but not essential.

If you think you might be a good fit for our small, fun and highly motivated lab, please email me to find out more.


References:

O’Neill et al., Curr Biol, 2008

O’Neill & Reddy, Nature, 2011

Feeney et al., Nature, 2016

Putker et al., ARS, 2017