Innovating research, policy and education in synthetic and systems biology

SynBioBlog: Building Human Artificial Chromosomes on the other side of the world

“I am just off to Japan to do some experiments.” This was the easiest way I could explain to my family that I was going to Japan to learn how to synthesize artificial chromosomes.

I joined the University as a Postdoctoral Researcher in the lab of Prof. Bill Earnshaw, funded through the UK Centre for Mammalian Synthetic Biology. We are working on a project that uses Human Artificial Chromosomes (or HACs) to understand the differences in functional chromatin states between the centromere and the flanking heterochromatin.

In April 2017 I visited the lab of Prof. Hiroshi Masumoto, a leading expert in the HAC field and a long-standing collaborator of Prof. Earnshaw based at the Kazusa DNA Research Institute in Kisarazu (Japan). The Masumoto group specializes in HAC synthesis through the transfection of human cell lines with BACs (Bacterial Artificial Chromosomes) containing long DNA repeats. Their goal is to improve the stability and efficiency of HACs so that, in the future, they could be used as vectors for gene delivery for treating human diseases.

Profs Masumoto and Earnshaw pioneered the creation of the first human chromosome with a conditional centromere: in this system the centromere (the region of a chromosome responsible for the correct segregation of chromosomes in daughter cells during cell division) can be suppressed or bound by specific chromatin modifiers expressed as fusion proteins with special targets. This system allows us to study the effects of changes in the epigenetic landscape on centromere function.

I spent two weeks at Kazusa DNA Research Institute learning cloning techniques from experts in the HAC field. I will now use what that knowledge to build a new HAC with two binding domains suitable for targeting with fusion proteins; one domain at the centromere and the other one at the flanking heterochromatin. This would help to understand how the different regions interact with each other.

During my trip I had the chance to exchange ideas with many people and to strengthen the relationship between our groups, both from a scientific and personal point of view. I experienced that even when there are cultural or linguistic barriers it’s easy to communicate with collaborators who are willing to share their knowledge and who are as passionate about their job as you are.

This journey had a great impact on both my knowledge and my motivation: there’s always something new to learn, especially on the other side of the world.

 

Dr Elisa Pesenti, Postdoctoral Research Associate, School of Biological Sciences

Photo: Elisa (centre) and the her hosts, the Masumoto lab under the cherry blossom