Automated Zebrafish Screening for Myeloid Leukemia Drug Discovery
In this interview, NewsMedical speaks with Elspeth Payne and Alexandra Lubin of the UCL Cancer Institute, who discuss how they are using zebrafish modeling to study the development of myeloid leukaemias.
Could you introduce yourself, what you do and briefly describe your research?
Elspeth Payne: My name is Beth Payne and I am a clinician-scientist. I work on myeloid diseases in the laboratory and take care of patients in the hospital; my laboratory works on blood cancers, in particular myeloid malignancies. We are using a combination of zebrafish modeling and drug screens alongside primary patient material to try to investigate better ways to understand the development of myeloid leukemias and the different ways we might deal with them in the future.
Alexandra Lubin: My name is Alex Lubin. I’m a post-doctoral researcher in Beth Payne’s lab. I work on zebrafish models of myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML). Drug screening is my main project and I plan to do drug screening in zebrafish tail hematopoietic stem cells to look for synthetic lethality.
How did you perform zebrafish analysis before using Athena software?
Alexandra Lubin: When I look at stem cells in my drug screen, I try to find a number change. To do this manually, all individual fluorescent cells must be counted in the tail. This means you have to take each fish under a microscope, scan through them and count them, which is very time consuming. For this reason, we started looking for an automated approach.
What challenges do you face in getting the data you need?
Beth Payne: We have developed drug screening methodologies, and while zebrafish is an excellent model for this, getting the right throughput has been difficult. Although there are many different platforms that one can use, they tend to offer tailor-made solutions for the way you analyze data. That means it’s expensive and time-consuming to develop a process that works for your goal.
When did you switch from manual imaging and image analysis to looking for automated solutions?
Beth Payne: We still use a lot of manual imagery because certain situations require its use. With regard to automated screening, we have been looking for a solution for probably five to ten years.
What are the main challenges when sampling with a manual workflow?
Alexandra Lubin: The main challenge with the manual method is that it takes time. It’s not particularly difficult to do, but it does involve spending hours and hours in front of microscopes. The other main problem with this is that you can’t get large numbers of samples. When you want to run something like a drug screen, the power comes from the ability to analyze many samples.
Image credit: IDEA Bio-Medical
What has this technology brought to your laboratory?
Beth Payne: What has been useful for this system is that we use it for all indications rather than just drug screening. For example, if we have a transgenic or even an in-situ that we want to image and look at that in detail in high content, we would use the Athena rather than doing it manually.
The other advantage of the system is that it is flexible and you can optimize it relatively quickly for a different test because the system is user-friendly. The company offers a lot of support to try to help us when we run into difficulties.
I would say overall it allows us to power our experiments much better because instead of just using 20 embryos, we can use 200 for the same processing time. Overall, it offers more flexibility.
Azo: When you started working on the Athena software, how long did it take you to be independent and productive?
Alexandra Lubin: When I first encountered Athena software, it was in full development. This resulted in many discussions with IDEA Bio-Medical about what we wanted the software to do, what would be useful, and highlighting areas for improvement.
Once it was operational, the transition time between the first use of the software and its complete independence was relatively short.
How does this compare to other instruments you use, for example compared to manual microscopes?
Alexandra Lubin: It was a unique experience in that we had more contact with IDEA Bio-Medical than we usually would. I’ve never used another system like this, so I don’t really have a direct comparison, but it’s great software and extremely handy.
How long does it take you to analyze all your fish samples and how does that compare before?
Alexandra Lubin: When performing these experiments manually, we can only screen about 100 fish at a time. However, it takes a long time, but once we start using the Athena, we can increase this number.
The number of fish I select depends on their behavior because anyone who works with zebra fish will know. It is possible to screen hundreds (of fish) in a short time because it only takes about 30 minutes from loading the plate to getting results for a hundred fish, whereas previously it took a whole day.
What do you do when you need help using the software? Who supports you and how?
Alexandra Lubin: When I need help with the software, I contact the IDEA Bio-Medical team. They were really helpful and offer a collaborative partnership. I provide them with images; they provide us with support – it works seamlessly.
When did you think the Athena software was useful for your research?
Alexandra Lubin: When I started this drug screening, we knew we had to introduce automation because it was not going to be possible to manually screen thousands of compounds. When we started looking at different methods, it became clear how easy the system was to use and how flexible it was. Also, we were attracted to the fact that Athena allowed us to branch out and switch it up if we needed to.
Where do you see your work going next and the impact?
Beth Payne: I think that certainly opened the door to making more and more screens. Perhaps we could now be able to conduct more ambitious types of screens where we could use, for example, more than one fluorophore or more than one genotype at the same time, because the time required for screening is so much more short and more efficient as you can introduce more variables.
About Dr. Elspeth Payne
Dr Elspeth Payne is a Senior Clinical Investigator/Clinical Consultant at the UCL Cancer Institute. His laboratory at the UCL Cancer Institute is dedicated to the study of inherited disorders of bone marrow failure and leukemia, and uses zebrafish to model these diseases. Dr. Payne is also a clinical hematologist at UCL Hospital, where she treats people with blood disorders including leukemia and bone marrow failure.
About Dr. Alexandra Lubin
Dr. Lubin is a post-doctoral researcher at the UCL Cancer Institute where she uses zebrafish to study myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), with the aim of developing new therapeutic treatments. Previously, she obtained her PhD in Chemical Biology from Imperial College London after studying Chemistry at the University of Cambridge.
About IDEA Bio-Medical Ltd.
IDEA Bio-Medical was founded in 2007 through a partnership between YEDA (the commercialization arm of the Weizmann Institute) and IDEA Machine Development (an innovation center).
IDEA Bio-Medical is a company specializing in automated microscopy and image analysis for life science researchers. IDEA’s products, the Hermes Imaging System and Athena Image Analysis Software, have contributed to over 100 scientific publications in peer-reviewed magazines, supporting high-impact science globally .
IDEA Bio-Medical is focused on empowering zebrafish researchers to provide them with a reliable and robust solution for automated and unbiased analysis of zebrafish images by applying company knowledge and specialties.
IDEA has developed new deep learning-based image analysis software for in vivo zebrafish experiments. The software automatically detects the outline of the zebrafish and its internal organs in brightfield without any user intervention. The identified anatomy is coupled with fluorescence channels to allow anatomy-specific study of fluorescence changes. It is an affordable, user-friendly system designed specifically for reliable, automated image-based analysis of zebrafish.
The software is suitable for researchers who only image a handful of fish per week, as well as researchers who image hundreds and thousands of fish in multi-well plates for large scale displays. Likewise, the software is available as a standalone product and accepts microscopy images in multiple image formats, including proprietary formats. Thus, all researchers using manual microscopes or automated systems from other vendors can easily use IDEA’s Zfish software to extract quantitative and meaningful information from their Zebrafish images.
more information can be found here: https://idea-bio.com/products/zebrafish-image-analysis/