Thomas Rutkowski: Cell Biologist

IMACS chats with Thomas Rutkowski, Assistant Professor in the Department of Anatomy and Cell Biology at the University of Iowa Carver College of Medicine. Prof. Rutkowski received his Ph.D. in cell biology from UC San Francisco and his B.S. in biotechnology with a minor in chemistry from the University of Delaware. He completed his post-doctoral fellowship at the Howard Hughes Medical Institute/University of Michigan. Prof. Rutkowski is also an alumnus of Project MEGSSS of St. Louis, Missouri, the sister program to Project MEGSSS of Broward County, Florida. The latter became IMACS in 1993. All three programs share a common curriculum that teaches students how to think critically using logic and reasoning.

Tell us what you’re currently working on in the lab.

My lab studies how cells respond to perturbation (“stress”) in the endoplasmic reticulum (ER). Sensing ER stress and responding appropriately is essential for the development and normal function of many different cell types, and dysregulation of the response contributes to a number of human diseases. We have two main interests. The first is understanding how ER stress contributes to fatty liver disease (FLD), which is the most common liver disease in the western world. FLD is latent and reversible in most people, but can progress to hepatitis, cirrhosis, or liver cancer, which are all irreversible. We have evidence that the ER stress response fundamentally alters how fat is metabolized in the liver, and that these alterations might contribute to FLD.

Our other interest is in understanding how the ER stress response senses the nature, strength, and persistence of the stresses that activate it, and then alters cell physiology to generate the appropriate response. For example, the ER stress response is activated both in immune cells when they are stimulated to produce antibodies, and in the liver after a meal—two very obviously different stimuli. What makes the ER stress response in the liver cell different from the response in the immune cell? This project actually has a significant mathematical component, and we are collaborating with a professor in the department of mathematics to build a mathematical model of the ER stress response. We will use the model to predict how the cell will respond to stresses of different types, thereby (hopefully) understanding how the signaling networks of the response are wired.

What are some of the potential applications of your research?

The simple answer to this question is that if we understand how cellular stress responses alter fat metabolism in the liver, then we will better understand how conditions like obesity, alcoholism, and hepatitis C infection lead to liver dysfunction and liver cancer, and ideally be able to prevent these problems. With the number of obese adults in the U.S. rapidly approaching one in three (not to mention the comparatively smaller but still significant numbers of alcoholics and hepatitis C patients), understanding and treating fatty liver disease and its downstream consequences is a huge challenge.

Of course, the larger reality is that basic research often comes with substantial but unforeseen rewards. By understanding basic cell biology we ultimately gain insight into many diseases, as well as normal human biology. A classic example I like to give is the MutS gene—which was first identified by a group studying DNA repair in bacteria, which would seem to most to be a highly esoteric topic with little practical value. However, the human equivalent of this gene later turned out to be involved in hereditary colon cancer. The rewards that come from simply asking how cells work, while perhaps harder to pin down, are probably far greater in the long run than anyone can imagine.

How did your experience in Project MEGSSS studying what is also the IMACS curriculum influence your path from high school to your present career?

I think in two ways, one somewhat abstract and the other fairly concrete. I think the abstract influence was in helping me to realize that my intellectual potential was far greater than I’d appreciated. In fact, I think most people never have a moment where they realize how limitless their own potential is, and that is a shame. When you go from being bored to death by long division in a traditional elementary school curriculum to learning college-level logic—and realizing that you are in fact learning it—it suddenly seems more reasonable to think big: big ideas and big aspirations. In this kind of curriculum, you are also exposed to other students who have already hit upon this realization. Then, as now, I think it stimulates my own thinking to be exposed to those who think about things on a wholly different plane, with incredible depth and creativity. Being a scientist, it is clear that big ideas are what move progress forward. MEGSSS was really my first exposure to the world of big ideas and creative thinkers that has (hopefully) shaped my initial inclinations toward science and how I’ve approached it since I’ve become a practicing scientist.

The other more concrete influence is in how we are using mathematics to inform our understanding of biology. In our quest to understand how cellular stress pathways work, one of the approaches we are taking is to develop a mathematical model of the stress pathway. By that I mean that each of the steps in the process is replaced by a differential equation that (ideally) accurately describes it. The point of this process is to develop a dynamic mathematical representation of the response that allows us to do computational experiments that we cannot do in real life, and so learn more about how the stress response works as a complex unit. Many biologists shy away from this kind of investigation, because they don’t intuitively appreciate how broadly applicable math is to problems in other areas and they aren’t comfortable with the language. Admittedly, we are collaborating with a mathematician to help us with our modeling, but I think that programs like MEGSSS and IMACS makes students much more aware of how diverse a field mathematics is, and also makes them so much more comfortable with the language, and willing to apply it elsewhere.

You’re a parent with a mathematically precocious child. What are some of the activities you engage in as a family to help foster that talent?

We ultimately try to expose our children to new ideas (mathematical and otherwise) and challenge them to reason through problems they don’t understand without pushing so hard as to turn them off. As my mother used to say, ”Use what you know to figure out what you don’t know.&rdquoMath has to be fun; learning has to be fun. Opportunities present themselves if you just look around. For example, we used the weather changes to illustrate the concept of rate of change. Here in Iowa we are blessed, or perhaps cursed, with four very distinct seasons. In the summer and winter months, the temperature doesn’t change much over time, but it changes quite rapidly from early fall to late fall, or early spring to late spring. Notice how the temperature might be warmest in the summer and coldest in the winter, but it changes the most in the spring and fall? Differential calculus at work, and hopefully introduced in a low-key way. Our primary goal as parents is to do whatever we can to keep them interested in math (and learning in general); if we can successfully do that, I hope they’ll naturally take to whatever curricula they are exposed to. Of course now that our oldest is entering third grade, and getting to the point where boredom with his regular math curriculum is starting to be a problem, we have had to look more actively for ways to foster his interest. I vividly remembered my exposure to logic and number theory in my first summer with MEGSSS (after fifth grade) and have since ordered those beginning books for him.

There is a lot of talk about the challenges the US faces in math and science education. From your point of view as a professor and a parent, what actions need to be taken to help US students become competitive again in the new global environment?

The U.S. is far and away the world leader in scientific research, which makes the mathematical and scientific illiteracy of the general population all the more discordant and alarming. We absolutely cannot sustain our technological edge in this environment—partly because we will no longer continue to produce talented scientists and mathematicians; and partly because a population that does not understand math and science will not support them intellectually or financially. A majority of Americans do not accept the idea of evolution—that all life arose by descent with modification from a common ancestor—despite the fact that it is the central organizing principle in biology, paleontology, and, importantly, medicine, and is one of the best supported scientific theories ever devised. A large minority of Americans do not accept that human activity is warming the planet, despite this too being an extremely well-supported theory and having reflected the consensus scientific view for nearly 20 years.

Where does this illiteracy come from? I think it ultimately arises from the fact that science (and math) represent fundamentally unique ways of thinking about the world that are simply not well-taught in schools. Science is not knowing the difference between igneous rock, sedimentary rock, and metamorphic rock. It is not repeating some ”experiment&rdquothat’s been done thousands of times over by millions of students with a prescribed result. Science is inquiry. It is observing the world, asking a question, forming a hypothesis, testing the hypothesis, and discarding the hypothesis if the test falsifies it, or moving forward with it if the test supports it. Every student learns this as ”the scientific method,&rdquobut how many get to put it into practice, to address a question to which the answer is unknown? How many science teachers make this kind of investigation the centerpiece of their curriculum, versus simply presenting a series of facts that must be memorized and ”labs&rdquothat must be suffered? Knowing that, as a scientist I am learning the answers to questions that have never been answered before, however big or small, is one of the true excitements of my vocation.

The same applies to math as well; math is not a worksheet full of arithmetic problems. It is a language that can be applied to real world problems, and requires its own way of thinking. There are teachers who approach science and math in this way, but I am convinced they are few and far between, and many others who want to probably feel they cannot, lest their students perform poorly on standardized tests. That people are not generally trained to think this way is evident from our national discourses. Debates are driven by ideology, with every viewpoint given equal weight. Arguments are made by assertion and evidence is cherry picked to support a preformed viewpoint. This is totally antithetical to scientific thinking, where the evidence drives the viewpoint and the viewpoint is subject to change based on the weight of that evidence. If science and math education in this country were geared toward teaching those ways of thinking, rather than toward the accumulation of information needed to pass a standardized test, I think not only would the population be more scientifically literate, and not only would we maintain our scientific edge, but we would also have much better informed and more productive dialogues on the issues facing society.