Currently serving as the Director of the Structural Biology Initiative at CUNY’s Advanced Science Research Center, and a Professor of Chemistry and Biochemistry at the City College of New York, Kevin Gardner has been studying the microscopic world of cells and cellular proteins over the last two decades. Ahead of his talk tomorrow night for the Secret Science Club event, I spoke with Professor Gardner about what questions he’s trying to answer, the role of technology in the field of structural biology, and his favorite geek thing to do in NYC…
Why did you decide to study structural biology? What questions are you trying to answer?
I love structural biology as someone who grew up really wanting to figure out how things work mechanistically and visually in the biological world, particularly at being able to understand how proteins / DNA / RNA work together at an atomic or molecular level. Structural biologists draw on this by being at the intersection of biology, chemistry, and physics: we are inspired by biology’s problems, rely on chemistry’s intuition to understand how atoms interact with each other, and use physics’ high-end techniques to determine atomic structures of cellular machinery.
With the problems my research group and I are trying to answer, we’re fundamentally interested in knowing how cells can sense and respond to changes in the environment around them. This has given us insights into things that seem pretty separated from each other, ranging from figuring out how human cells sense changes in the level of oxygen around them to asking how plants and bacteria detect changes in blue light levels. This said, evolution provides powerful links between these stories – nature has conserved the use of some common machinery for both – and in turn, our answers have fueled a series of applications as interesting as the research itself.
What is the relationship between a gene and a protein? How do their functions differ when it comes to the development of human traits?
The gene is the DNA message which encodes the sequence for the protein – the former is in many regards carrying the message, but the latter is the actual cellular machinery which determines whether a cell lives or dies (and accordingly, whether the gene is passed to the next generation of cells)
How is your research on proteins contributing to the advancement of cancer treatments?
Most directly, we’ve solved the experimental structures of certain proteins involved in the cellular response to low oxygen (“hypoxia”) which is used by human cells and many other organisms. This system has received a lot of attention recently – these “HIF” proteins and the way that O2 controls them was the focus of the 2019 Nobel Prize in Physiology or Medicine – as has its importance in controlling the development of certain illnesses, particularly cancers, when its normal regulation is stopped for various reasons. My research group solved the structures of parts of these HIF proteins and identified novel sites where we thought they might be controllable by new small molecule drugs. Working together with a talented research team of my own and several colleagues – most notably, Rick Bruick (UT Southwestern Medical Center) – we put this idea to the test and saw positive enough results to help lead to the formation of a biotech company in 2011 which further improved the efficacy of our initial compounds and saw them into clinical trials. Merck is now following up this work after purchasing that company in 2019.
Computer technology has helped scientists model and predict the shape (aka “the fold”) of proteins. Why is this such an important area of study? How does computer modeling of protein folds help us understand the mechanisms of disease?
This is an important area of advancement, as many of the experimental methods that we rely on as structural biologists are often challenging to apply to new proteins or cellular machines. This is due to a slate of technical issues – ranging from needs for relatively large amounts of pure samples, to simply needs for our molecules to “behave” in ways that we sometimes don’t fully understand – and leaves all of us with our own wishlists of new targets we’d love to study. Computational methods to model these systems provides a way to help us address some of those concerns, as well as helping provide other scientists with ways to begin developing atomic-resolution hypotheses about how these systems work in normal biology and disease. To be clear, nature has dealt us plenty of surprises in structural biology, so experimental results are always superior to computational models in my view – but anything that can help those experiments get dreamt up and tested is an important piece of the field.
As a New Yorker, what’s your favorite place to geek out in NYC? Where do you go for inspiration?
To the Secret Science Club, of course! Seriously, this is a great forum which brings scientists from across fields together to share their work with the public. More broadly, New York City is tremendously fortunate to have a tremendous slate of seminars at our local area universities, medical centers, academies, and beyond which are outstanding ways for professional scientists to be able to learn about the latest developments in their fields. Many of these are open to the public, and an increasing number are live-streamed as well. These venues provide a great source of both places to geek out and find inspiration; beyond this, I’m always amazed by our great collection of art museums and places to get out for a run – providing plenty of inspiration to me for the mind and body.
Meet Kevin Gardner tomorrow night for the Secret Science Club talk at the Bell House in Brooklyn. Details here.