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The molecular basis of ascidian whole body regeneration
genesis ( IF 1.5 ) Pub Date : 2023-07-14 , DOI: 10.1002/dvg.23537
Megan J Wilson 1
Affiliation  

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).

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FIGURE 1
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The Wilson Lab group celebrating the submission of Beri Temiz's PhD thesis (April 2023). From left to right: Sevanaia Seeto, Megan Wilson, Rachel Cannon, Beri Temiz, Devon Gamble, Bridget Fellows, and Justine Gupaz.

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).

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FIGURE 2
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Our research has used a combination of molecular, genomics, and histological tools to study whole-body regeneration. (a) Section through a Botrylloides diegensis whole colony (Blanchoud et al., 2017; Zondag, 2016) stained with Giemsa. (b) Ascidians (solitary and colonial) growing on a rope in the Otago Marina. (c) Schema summarizing Zondag et al., 2019. HDAC inhibition stops regeneration at Stage 3. (d) Screenshot highlighting genome sequencing, annotation, and transcriptome research. Shown is the g11778 (AEBP1) gene, identified as being differentially expressed during whole-body regeneration (Zondag et al., 2016). Sequencing reads have been aligned to the genome (Blanchoud, Rinkevich, & Wilson, 2018; Blanchoud, Rutherford, et al., 2018). This gene is largely expressed only during regeneration.

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.



中文翻译:

海鞘全身再生的分子基础

由于我对分子生物学的浓厚兴趣,我攻读了生物化学和遗传学学士学位。为了获得荣誉学位和博士学位,我深入研究了西格玛因子:一种与致病菌铜绿假单胞菌的感染和毒力有关的基因调节蛋白。

我进入发育生物学的旅程植根于个人的好奇心。在攻读博士学位期间,我试图了解我哥哥的遗传性疾病,即结节性硬化症 (TSC),这种疾病表现为影响肾脏、大脑和皮肤等多种器官系统的良性肿瘤生长。肿瘤在特定器官中令人费解的发生以及个体之间症状的显着差异促使我深入研究发育生物学领域。

这促使我为博士后职位开辟了一条新的道路,加入了澳大利亚昆士兰大学分子生物科学研究所的发育生物学家 Peter Koopman 教授的团队。在那里,我研究了哺乳动物性腺发育的分子遗传学。

随后,我于 2005 年作为博士后研究员回到奥塔哥,重点研究进化和发展。在 Peter Dearden 教授的指导下,我利用蜜蜂和果蝇模型,将我的研究兴趣扩展到基因调控、发育及其进化背景。

本来,我打算用Ciona研究发育基因的进化。海鞘是与脊椎动物谱系最接近的无脊椎动物群,为早期脊椎动物发育途径的进化提供了宝贵的见解(Heenan et al., 2016)。在参观尼尔森的一家海洋研究所时,我了解到了葡萄孢属,以及它们在短时间内从血管外衣的一小块碎片再生出全新成虫的令人印象深刻的能力(图 1)。

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图1
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威尔逊实验室小组庆祝 Beri Temiz 博士论文的提交(2023 年 4 月)。从左到右:Sevanaia Seeto、Megan Wilson、Rachel Cannon、Beri Temiz、Devon Gamble、Bridget Fellows 和 Justine Gupaz。

我们的研究重点是了解脊索动物模型(特别是Botrylloides)中驱动再生过程的机制。我们首先通过从头转录组分析探索参与全身再生的分子途径(图 2;Zondag 等人,2016;Meier & Wilson,2022)。然后,我们对基因组进行了测序和注释,以扩展我们对被囊动物基因组特征和进化关系的了解(Blanchoud,Rutherford,et al.,2018)。此外,我们正在研究表观遗传调控在全身再生中的作用,并发现组蛋白脱乙酰酶活性对于再生过程至关重要(图2;Zondag et al., 2019)。

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图2
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我们的研究结合了分子、基因组学和组织学工具来研究全身再生。(a) 用Giemsa 染色的Botrylloides diegensis整个菌落切片(Blanchoud 等,  2017;Zondag,2016)。(b) 在奥塔哥码头的一根绳子上生长的海鞘(独居和群居)。(c) 总结 Zondag 等人,  2019 年的模式。HDAC 抑制在第 3 阶段停止再生。(d) 突出显示基因组测序、注释和转录组研究的屏幕截图。显示的是 g11778 ( AEBP1 ) 基因,该基因被鉴定为在全身再生过程中差异表达(Zondag 等人,  2016)。测序读数已与基因组进行比对(Blanchoud, Rinkevich, & Wilson,  2018;Blanchoud, Rutherford, et al.,  2018)。该基因仅在再生过程中大量表达。

最近,我们利用单细胞和 ATAC 测序等基因组学工具来揭示再生过程中基因调控的复杂控制。我们的工作得到了奥塔哥大学研究补助金、院长遗赠补助金和新西兰皇家学会马斯登基金的资助。

我学术生涯中最充实的方面之一是指导和监督研究生。到目前为止,我已在我的实验室内指导了 9 名博士生、13 名荣誉生、5 名 PgDipSci(科学研究生文凭)和 7 名硕士生。值得注意的是,其中三名学生是研究Botrylloides再生的女性——Lisa Zondag、Rebecca Clarke 和 Beri Temiz 都完成了博士学位。分别于2016年、2022年和2023年获得学位。值得一提的是,这三位女性都是第一位博士生。自 20 世纪 50 年代 Beryl Brewin 博士的研究以来,许多候选人在新西兰与海鞘类相关的研究中完成学位。

尽管最近带来了重大挑战,包括大流行、隔离和资金削减的影响,但我坚信,新西兰新西兰的海鞘和海洋科学研究仍然存在巨大的机会。

更新日期:2023-07-14
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