The Humans of the Wyss (HOW) series features members of the Wyss community discussing their work, the influences that shape them as scientists, and their collaborations at the Wyss Institute and beyond.
When she’s not designing and finessing her garden, Instrumentation Engineer Susan Marquez is designing and finessing a compact epifluorescence microscope that’s being used for the Wyss Biostasis Project. The project aims to extend the “golden hour” of survival between injury and access to treatment by slowing metabolic processes to prevent a harmful response from the body’s own immune system. Learn more about Susan and her work in this month’s Humans of the Wyss.
What are you working on?
I am working on the Biostasis Project with Richard Novak in Don Ingber’s lab. The initial goal of the project is to discover and develop drugs that slow biochemical processes to extend the golden hour of survival between injury and access to treatment. As an instrumentation engineer, my role within the project is to create instruments that allow us to truly understand the impact our drug candidates have on metabolism in a high throughput manner. The tool I’m developing is a customized compact microscope that can read six well plates with three excitation wavelengths and fits inside a standard tissue culture incubator (seen in the photo on the right).
What real-world problem does this solve?
Sometimes, when soldiers are injured on the battlefield, they die before they can access treatment. The greater objective of the Biostasis Project is to extend that lag time by slowing down biological processes that can lead to further harm, like bleeding to death or the onset of sepsis, and then speeding them back up once the patient is somewhere that treatment is available. Sometimes, the immune system’s response is worse than the initial injury, and we want to protect people from that.
The compact microscope I’m developing solves logistical issues on the way to reaching this goal. One way we are trying to test the efficacy of potential drugs to extend that golden hour of survival is by measuring metabolic activity in cells and then measuring the effects of drug candidates to see how that activity changes. Can we slow down the activity for a set amount of time and then bring it back up to speed? The microscope helps to measure this activity in an effective way. Its customizability allows us to control the temperature, humidity, and carbon dioxide levels in order to ensure optimal conditions during the entire experiment. We can tune into the wavelength of our drugs, our cells, and our reporters so that we can maximize the efficiency of the data. The microscope’s advanced imaging capability allows us to get a much better understanding of the impact of our drugs than an off-the-shelf product would.
What inspired you to get into this field?
I joined the Wyss several years ago to work on the Human Body on a Chip project, which aims to integrate multiple Organ-on-Chip systems to mimic the whole human body to accelerate the assessment of drug safety and efficacy. The promise of using Organs-on-Chips to speed therapeutic developments while minimizing animal testing was really motivating. One of my contributions to that program was engineering a compact microscope to visualize Organs-on-Chips inside our tissue culture incubator. I hadn’t done this exact type of work before – my degree is in electronic materials and for the first ten years or so of my career I made semiconductors and superconductors. When I started in the spectroscopy division, I received a lot of on-the-job training in order to transition into what I do now. The Human Body on a Chip project is what got me into working with compact microscopes. I found the initiative so fascinating and inspiring that I was eager to take on the work.
The microscope used to further the development of the Human Body on a Chip was sufficient for that project, but I always wanted to make it better. In a process that felt unique to the Wyss, the Biostasis team was assembled from interdisciplinary researchers who had worked on a variety of projects both at the Wyss and elsewhere. I was excited that the Wyss’ culture of self-assembly enabled me to further develop the microscope for a completely different application, since this project required a much more sensitive instrument with better image quality and more features, such as fluorescence capability. We’ve been through a couple of versions now. I have added multi-wavelength excitation to our incubator microscope, enabling ratiometric analysis of metabolic markers such as ATP/ADP. Now we have a robust version that’s providing good data. My current goal is to create and adapt instrumentation that allows us to better understand intracellular processes, which will ultimately lead to biomedical solutions.
What continues to motivate and excite you?
A lot my motivation is personality-based. Richard Novak has been a great mentor. His excitement about everything is so infectious and he keeps the whole team involved in the project and driven to solve whatever challenges lie ahead.
I am inspired working with my team to synthesize mechanical, optical, electronic, and software components into systems that produce valuable information. It is most rewarding to share in the moment when a colleague sees a sample’s readout on an instrument that I have helped to optimize for our application. For example, my colleague Tiffany Lin will often come to me when different tools around the lab are giving her trouble – maybe the carbon dioxide levels aren’t staying consistent or the definite focus is not working. But by using my instrument, we are able to see exactly what Tiffany wants to see, alleviating her from a lot of effort and frustration. That feeling that you’re making something that is helping your colleagues and allowing the whole project to move forward is indescribable. I love seeing their faces when we reach an “ah-hah” moment together.
How has your previous work shaped your approach to your work today?
I have a strong commitment to public health. My previous work focused on measuring exposure of farm workers to pesticides for the National Institute of Environmental Health Sciences and detecting trace levels of chemical and biological threats for Homeland Security Advanced Research Projects Agency. Working at the Wyss enables me to continue my efforts to advance public health.
When you’re not at the Wyss, how do you like to spend your time?
I love to be outdoors and to travel. Some of my happiest weekends are spent reshaping and expanding my flower gardens and vegetable beds. My landscaping vision is inspired by visiting botanical gardens, so far within North America and Europe. The botanical gardens in Montreal were a favorite of mine, probably because I didn’t expect to find so much color and variety so far north. There are also some beautiful gardens in Colonial Williamsburg. The Gardens of Versailles are amazing – they’re on a whole different level!
If you had to choose an entirely different career path, what would it be?
Landscape architect. I just watched the movie A Little Chaos about the woman tasked with designing one of the gardens of Versailles. I would love to have her challenge of creating the gardens of Versailles, especially with that unlimited budget!
I’m drawn to both the aesthetic and the scientific facets involved in landscape architecture. I love reading books about the principles of design and how you should put plants in layers for the seasons, but I also love reading about how peas fix nitrogen in soil. All of these pieces fascinate me.
What does it feel like to be working on cutting-edge technology that has the potential to have a real and significant impact on people’s lives and society?
It is rewarding to make a difference, whether it is for a patient seeking treatment, a doctor making a diagnosis, or a researcher aiming to better translate their finding into medical practice. I’m glad to be doing this kind of work.