ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping researchers promote themselves alongside their papers. Lorena Maili is first author on ‘ Facial analytics based on a coordinate extrapolation system (zFACE) for morphometric phenotyping of developing zebrafish’, published in DMM. Lorena conduced the research described in the article while a graduate research assistant (predoctoral student) in the lab of Dr Jacqueline Hecht (in collaboration with Dr George Eisenhoffer) at The University of Texas MD Anderson Cancer Center, Houston, TX, USA. She is now a postdoctoral fellow in the lab of Dr Paul Trainor at Stowers Institute for Medical Research, Kansas City, MO, USA, investigating genetic regulation of craniofacial development.
Lorena Maili
How would you explain the main findings of your paper to non-scientific family and friends?
Structural anomalies affecting the head and face are the most common defects present at birth. In order to improve the prognosis and develop new therapeutic approaches for patients, there is a critical need to understand how these anomalies occur during embryonic development. One major challenge in this endeavour is the inability to access embryos in utero without disrupting development. Zebrafish embryos develop externally, are transparent, and share many anatomical structures and genes with mammals, making them an ideal animal model for in vivo developmental studies. Here, we developed a method called zFACE, to visualize zebrafish larvae ‘face on’ by suspending them upside down in agarose and taking confocal microscope images of the facial region. This view allows us to see and landmark (or place points on) critical anatomical structures, which are then used as coordinates to automatically calculate 39 distances, areas and angles. (This is similar to how facial recognition works.) The measurements that zFACE produces can be used to detect subtle differences in specific regions of the face, or with the implementation of other free software, to statistically test changes in overall face shape. We hope that this easy to use and semi-automated method will be utilized by zebrafish researchers to obtain standardized quantitative information of facial differences.
“The zFACE method described and tested in our paper can be used as a quantitative tool to uncover previously unappreciated craniofacial alterations in zebrafish models.”
What are the potential implications of these results for your field of research?
The zFACE method described and tested in our paper can be used as a quantitative tool to uncover previously unappreciated craniofacial alterations in zebrafish models. This approach will provide better detection of subtle differences that result from genetic or environmental perturbation. We anticipate that this approach will help unravel multifactorial contributions to structural birth defects, for which multiple factors, each with a small effect, are postulated to contribute.
What are the main advantages and drawbacks of the experimental system you have used as it relates to the disease you are investigating?
Although zebrafish share a lot of the same morphological structures during development, there are also differences. One drawback, for example, when studying cleft lip and palate, is that zebrafish have an ethmoid plate that is homologous to the secondary palate. A major advantage of zebrafish is the ability to obtain and analyse large numbers of embryos and larvae, and this can be very powerful and improve reproducibility of data. The integration of cell and molecular findings from zebrafish studies with human data will be instrumental in uncovering clinically relevant information to improve patient outcomes.
What has surprised you the most while conducting your research?
I was very surprised at how much better the morphometric data are at capturing and quantifying changes that are not visibly apparent, even to a trained eye. It's important to have an unbiased approach in classifying phenotypes that extends beyond the categories of normal and abnormal.
What do you think is the most significant challenge impacting your research at this time and how will this be addressed over the next 10 years?
We are making great strides in identifying genetic variants that potentially play an aetiologic role in complex disorders such as structural birth defects. However, understanding the biological relevance of these variants and the mechanistic underpinnings of how they contribute to normal or abnormal craniofacial development remains a future challenge and important focus. Development of high-throughput platforms that integrate automated quantitative approaches will be key to uncovering this important information.
“It would be very helpful for graduate students and postdocs to receive more guidance and formal training in skills beyond the bench that are necessary for a successful career […]”
What changes do you think could improve the professional lives of scientists?
It would be very helpful for graduate students and postdocs to receive more guidance and formal training in skills beyond the bench that are necessary for a successful career, such as grant writing, networking, mentoring, leadership and science communication.
What's next for you?
I am currently conducting postdoctoral research on mammalian genetic models of craniofacial disorders, with a focus on understanding the mechanisms that regulate neural crest cells during their differentiation into craniofacial bone and cartilage.
Lorena Maili's contact details: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Email: [email protected]
