The molecular basis of ascidian whole body regeneration

I studied Biochemistry and Genetics for my BSc, due to my keen interest in molecular biology. For my Hons and then PhD I studied, delving into exploring a sigma factor: a gene regulatory protein involved in infection and virulence in the pathogenic bacteria Pseudomonas aeruginosa.

My journey into developmental biology was rooted in personal curiosity. During my PhD, I sought to understand my brother's genetic disorder, Tuberous Sclerosis Complex (TSC), which manifests in benign tumor growth affecting various organ systems such as the kidney, brain, and skin. The puzzling occurrence of tumors in specific organs and the significant variability of symptoms among individuals drove me to delve into the field of developmental biology.

This led me to take a new path for a Post-doctoral position, as I joined the group of developmental biologist Prof Peter Koopman at the Institute for Molecular Biosciences, University of Queensland, Australia. There, I studied the molecular genetics of mammalian gonad development.

Subsequently, I returned to Otago in 2005 as a Postdoctoral Fellow, focusing on evolution and development. Under the mentorship of Professor Peter Dearden, I expanded my research interests to encompass gene regulation, development, and their evolutionary context, employing honeybee and Drosophila models.

Originally, I was planning to study the evolution of developmental genes using Ciona. Ascidians, representing the closest invertebrate group to the vertebrate lineage, offer valuable insights into the evolution of developmental pathways in early vertebrates (Heenan et al., 2016). While visiting a marine institute in Nelson, I was introduced to Botrylloides and their impressive ability to regenerate a whole new adult from a small fragment of the vascular tunic in a short time (Figure 1).

Our research focuses on understanding the mechanisms that drive regenerative processes in a chordate model, specifically Botrylloides. We started by exploring the molecular pathways involved in whole-body regeneration through de novo transcriptome analysis (Figure 2; Zondag et al., 2016; Meier & Wilson, 2022). We then sequenced and annotated the genome to expand our knowledge of tunicate genome characteristics and evolutionary relationships (Blanchoud, Rutherford, et al., 2018). Additionally, we are studying the role of epigenetic regulation in whole-body regeneration and have found that histone deacetylase activity is essential for the regenerative process (Figure 2; Zondag et al., 2019).

More recently, we have utilized genomics tools, such as single-cell and ATAC sequencing, to unravel the intricate control of gene regulation during the regenerative process. Our work has been funded by the University of Otago Research Grant, Dean's bequest grant, and the Royal Society of New Zealand Marsden Fund.

One of the most fulfilling aspects of my academic career is mentoring and supervising postgraduate students. So far, I have supervised nine PhD, 13 Honors, 5 PgDipSci (Postgraduate Diploma in Science), and seven Master's candidates within my laboratory. Notably, three of these students were women who studied Botrylloides regeneration—Lisa Zondag, Rebecca Clarke, and Beri Temiz all completed their Ph.D. degrees in 2016, 2022, and 2023, respectively. It is worth mentioning that these three women are the first Ph.D. candidates to complete their degrees while working with ascidians in New Zealand since Dr. Beryl Brewin's research in the 1950s.

While recent times have posed significant challenges, including the impact of the pandemic, isolation, and funding cuts, I firmly believe that there are still immense opportunities for further research in ascidian and marine science within Aotearoa, New Zealand.