From axolotls to zebrafish, discovery science is crucial
This is the first of a regular blog from Wellcome’s Science division. I hope to highlight some interesting research (not all necessarily funded by Wellcome), some research opportunities and some policy matters that affect biomedical science.
I’m going to start with the Science Division strategy, which was launched at the beginning of October, ten months after I started at Wellcome. The strategy has four pillars:
strengthening research capability
using knowledge effectively
promoting an environment in which research can flourish.
Underlying the strategy is the recognition that everything starts with discovery science – the creation of knowledge. We place emphasis on this for two reasons. First, because an understanding of how life works is important in its own right. Wellcome is well-placed – perhaps uniquely placed – to support such research. But the second reason, of course, is that it is from discovery science, and its effective use, that we come to understand disease and to develop ways to treat it.
Research that has saved a child’s skin. Literally.
The boy had lost 80% of his skin, and he was in a medically induced coma. As is now well-known, the team treating him took some of his few remaining healthy skin cells, introduced a normal version of the LAMB3 gene by means of a retroviral vector, cultured those cells, and then transplanted them onto the child. He now has 80% of his skin derived from genetically modified stem cells. He has returned to school and he can lead a normal life.
This inspiring achievement derives from many years of research on keratinocytes, beginning with Rheinwald and Green’s pioneering cell culture work 42 years ago and continuing with more recent work on epidermal stem cells.
Significantly, by using the viral integration sites in the regenerated skin as a form of lineage marker, the work revealed that almost all the regenerated skin was derived from the highly proliferative colonies identified in vitro known as holoclones. This suggests that these holoclone contain the epidermal stem cells that can sustain and, if necessary, replace the entire epidermis.
Going out on a limb
The potential of regenerative medicine is huge, of course, and there is much we still don’t know.
My colleague Andrew Chisholm and I are particularly interested in the ability of some animals to regenerate or repair large parts of their bodies. These include, at one extreme, the planarian flatworm, which can regenerate an entire animal from perhaps a hundredth of the original organism, or at the other extreme the amphibian limb or zebrafish heart.
I have been interested in limb regeneration since my PhD days, when I studied the development of the chick limb. It is now over 40 years since Vernon French, Susan Bryant and Peter Bryant put forward the polar coordinate model to explain regeneration in amphibian and cockroach limbs, and in the Drosophila imaginal disc
I sometimes wonder if it’s time for that model to be revisited, perhaps using the axolotl (Ambystoma mexicanum), a neotenic urodele threatened in the wild but (so far) flourishing in labs and home aquariums.
What else can discovery science reveal?
Regeneration is just one example of an area where our knowledge is poor and where discovery science has so much to offer our understanding of how the world works and in its potential for preventing and treating disease. My colleagues and I in the Science teams at Wellcome are keen to hear ideas in any other areas that the scientific community regards as important.
We’re looking for proposals that are exciting, bold and innovative, where the long-term outcome may not always be clear but where the intellectual benefits are obvious. As usual, we’ll consider these through our response mode schemes.
Alongside the schemes, we will continue to scope opportunities for strategic investment in specific areas. This work will now be supported by our new Science Strategic Advisory Group (SSAG).
This group is chaired by Tony Hyman and held its first ‘getting to know you’ meeting on 24 November. From this, it’s clear that the group will provide a really valuable forum to discuss all aspects of our strategy, as you’ll read in future blogposts. Watch this space.
Three films that are well worth watching
I went to the UK Contribution to Innovation in Global Health meeting and heard a fantastic talk by Dr Andrew Bastawrous.
And watch Wellcome’s film Learning from the liver how to regenerate (viewing time 60 secs) in which Sir Henry Dale Fellow Meri Huch explains her lab’s work on liver organoids. It’s so valuable to be able to study development and disease in three dimensions.
I’ve mainly focused on the first pillar of the Science division’s strategy – creating knowledge – in this blogpost. In the next, I’ll look at how Wellcome will strengthen research capacity.
I’m interested to know what you think. Any thoughts on holoclones, axolotls or Wellcome’s science team strategy, do let me know via Facebook, Twitter or LinkedIn.