Split pair: chromosomal segregation
Meiosis is still mostly uncharted territory, especially in mammalian eggs, and is of significant medical interest. Many of the chromosomal errors leading to pregnancy loss and genetic disorders like Down Syndrome occur during meiotic divisions in the oocyte stage. Though research suggests that these issues arise at this point in the process, how they come to be are still unknown. So and his team aim to create innovative technology to change the research and screening process from one based on dead specimens’ vector cells to a live study.
During each menstrual cycle, an oocyte resumes meiosis in the ovary and completes the first meiotic division to mature into a fertilisable egg. During this process, the nucleus breaks down and a spindle forms in the centre before moving to the oocyte’s surface, where it segregates the homologous chromosomes, eliminating half into the polar body and preparing the cell for intake of a second set of chromosomes in the case of fertilization. The role of cytoskeletal structures may lead to meiotic errors such as mis-segregation. Chromosomal segregation is driven by a spindle of microtubule network, and the structure’s incorrect positioning may capture the wrong chromosomes or interact in the wrong place. Separation or incorrect cohesion during the meiotic process can be influenced by cellular structure, molecular mechanisms, or even maternal age, and can lead to imperfect chromosomal pairings.
Within the context of the inner workings of meiosis, a critical question deals with chromosomal behaviour during the process, which has been impossible so far because pan-chromosomal markers only hint that there is a problem, but not which individual chromosome is the issue. Identifying particular chromosomes is necessary to rule out or diagnose different chromosomal diseases. This is particularly true in the oocyte stage, where the frequency of desegregation is considerably higher. So’s PhD project is analysing the development of chromosomes in human and mouse oocytes, and is hoping to incorporate live imaging systems to study how they move and interact with other bodies within oocytes.
In a clinical setting, the results will be invaluable for in-vitro fertilisation, which currently utilises a biopsy method, allowing the diagnosis of whether pre-mutational cells are viable or not. Biopsying oocytes ruptures the protective zona pellucida, which is physically risky. Therefore So’s live imaging method proposes using microinjections of tiny needles and sIRNA-based probes, which do not integrate into the genome and are safer for micromanipulation, yielding test results in 2-3 days or even mere minutes. The live imaging technique allows researchers to follow oocytes in vitro through the whole maturation process, chromosomal segregation and interactions with the exoskeleton, catching errors as they happen in real time. These molecular mechanisms are difficult to study, given the variety of biological aspects and rarity of human oocytes for study. Not only do researchers have to make do with a very limited number of specimens, oocytes do not mature well in isolation, making the required technology even more specialised.
So had initially been interested in chemistry in secondary school, even taking advanced studies in a chemistry lab at Chinese University of Hong Kong but kept being drawn back to biology. He reflects, “chemistry is obviously very important, but biology holds the keys to the basic human questions, and the implications for research in this field are more profound. We study things that everyone goes through from even before life begins—who wouldn’t be excited by that?”
Nick So won a Croucher Scholarship in 2016 for his post-doctoral research in oocyte biology at the Max Planck Institute for Biophysical Chemistry. He gained his first two lab experience at Chinese University of Hong Kong under the supervision of Prof KS Chan and Prof Tsang, also a Croucher scholar, during his high school education at La Salle College. By the time of the release of HKDSE results, he made a tough decision between studying chemistry, biology or medicine. He received his degree in Cell & Molecular Biology from Chinese University of Hong Kong. During his undergraduate study, he received 15 awards and scholarships including the Swire Scholarship 2013-2016 and the Fung Scholarship 2015-2016. He received excellent guidance from Prof Tsang and led a research project on the molecular and cellular mechanisms linking diabetes and breast cancer. He also collaborated with other labmates on the roles of different TRP channels in mouse embryonic stem cells and cardiac development.
To view So’s Croucher profile, please click here.