Examining avian sex chromosome dosage compensation

An animal’s sex can be determined by its chromosomes. In mammals (XX female, XY male), one of the X chromosomes in females is mostly switched off to balance gene expression, while in birds (ZW female, ZZ male) both Z chromosomes remain active in males, with only partial adjustments in gene expression. At the Roslin Institute, Dr Amir Fallahshahroudi investigated a microRNA on the avian Z chromosome that is predominantly expressed in males and may help fine-tune this balance. With access to expertise and facilities for chicken gene editing, he was able to delete this microRNA in vivo and study its effects in chickens. The results, published in Nature, reveal a new mechanism by which small RNAs regulate sex-linked genes in birds, showcasing how cutting-edge genetic tools can resolve long-standing questions about how males and females manage their genes.

1. Can you briefly describe your project at Roslin and how visiting the Roslin Institute supported your research?

We had previously identified a microRNA on the avian Z chromosome that is predominantly expressed in males and hypothesised it contributes to dosage compensation by repressing specific target genes. To test this, we needed to generate direct functional evidence through in vivo gene editing in chickens. Visiting the Roslin Institute made this possible, thanks to their unique expertise and infrastructure for avian gene engineering. Crucially, our work depended on access to the germ cell–ablatable chicken line (sterile surrogate host) maintained at the National Avian Research Facility (NARF), without which these experiments could not have been completed in a timely manner.

2. What unique resources, such as equipment, expertise, or bioresources did you access at Roslin, and how did these enhance your project?

My project relied heavily on the NARF, which provides the most efficient and reliable platform for generating gene-edited chickens globally. In addition to the NARF’s expertise and infrastructure, I also accessed the Bioimaging and Flow Cytometry facilities at Roslin, which supported my experiments.

4. As an early-career researcher, what were the key professional and personal benefits, such as new skills, publications, or international exposure, that you gained from the experience?

I conducted part of my postdoc at the Roslin Institute, which benefited my career on multiple levels. I acquired valuable technical skills and was able to test our hypothesis in vivo—work that led to establishing a new paradigm in avian biology. This research was published in Nature, significantly increasing my visibility in the field. During my time at Roslin, I also built new collaborations and lasting friendships. The international dimension of this experience further strengthened my CV, as mobility is widely recognised as an asset when applying for grants and academic positions. Overall, the experience played a crucial role in helping me establish myself as a principal investigator after my postdoc. I am now designing a new collaborative experiment with the Roslin Institute to investigate additional open questions in avian biology using gene editing.

5. What advice would you give to researchers interested in applying to attend a Visiting Researcher Programme at Roslin?

The Roslin Institute has a very open and collaborative atmosphere, with shared spaces where researchers often gather for lunch or informal discussions. My advice is to take full advantage of this environment—talk to people, introduce yourself, and actively expand your network. Don’t hesitate to reach out to researchers with overlapping interests. Knock on their door, invite them for a coffee, and share your ideas. In my experience, people at Roslin are approachable, supportive, and open to collaboration.