Genetics Interview #8: Dr. Alex Palazzo of The Daily Transcript

Our series of genetics interviews continues this week with another impressive scientist, Dr. Alex Palazzo of The Daily Transcript. Alex is a cell biologist currently at Harvard Medical School studying RNA and the endoplasmic reticulum. If you keep your eyes on his blog, he has some amazing pictures of these cellular components. His thoughts on science and the scientific life are also very insightful as are his answers to my interview questions.

1. When and how did you become interested in cell biology? How would you differentiate between cell biology, molecular biology, and genetics?

I think that I was always fascinated with the natural world. When I was 18, I read Richard Dawkin’s The Selfish Gene, and I fell in love with evolution and biology. Later at McGill University working as a research assistant in Dr. Morag Park’s lab, I was introduced to cell biology and the question of cellular locomotion. It was great. I would peer down at a dish of tissue culture cells and find a whole world down there. How did those cells move? How were they organized? How did they change their shape? You look at these “bags of molecules” and they are more complicated than our most sophisticated machines. I became obsessed with this idea. At that point, I started to get interested in the cytoskeleton, a dynamic scaffold in our cells that can rearrange itself in response to cellular signals. I read all the early papers on the assembly of the actin cytoskeleton – the works of the Mitchison, Pollard, Zigmund and Small labs. After undergrad, I ended up at Gregg Gundersen’s lab at Columbia where I worked on how the microtubule cytoskeletal network contributes to cell migration.

Cell biology is a philosophy. It’s looking at cellular behavior and determining how proteins collaborate to generate that behavior. Most of the techniques in cell biology involve cellular assays. Gregg had developed a fantastic wound-healing model to study how cells polarize, in this case, towards the wound, and then migrate to fill the wound. We could alter the cells by microinjecting morphogens or signaling molecules. We then analyzed the cells using microscopy or various biochemical methods. Using this methodology, we identified two signaling cascades that regulate two aspects of the microtubule cytoskeleton. Incredibly, most of the constituents of these two pathways had been identified previously by yeast geneticists. So by geneticists, I mean molecular geneticists who use genetically tractable organisms, such as yeast or fly, to tease out critical molecules involved in any given process. Many cell biologists and biochemists have conceded that of all the disciplines, molecular genetics has brought us more information than all the other disciplines combined. They figured out the cell cycle, the polarity signals, most of the players in DNA repair … you name it and they probably were the first.

Molecular biology, at least in the circle of scientists that I frequent, implies the study of DNA or RNA. How are genes turned on or off? What important elements are present within a stretch of DNA or RNA that gives it the capability of recruiting certain proteins? Presently I am studying how RNA is organized within cells … so I guess you can call me a molecular biologist. Now all these terms (molecular biology, cell biology and genetics) are very arbitrary. Go to any molecular biology department and it is full of cell biologists and molecular geneticists.

2. What research projects are you involved in now? How will they eventually apply to people’s everyday lives?

When genes get activated, they are copied or transcribed into messenger RNAs (or mRNAs). These molecules are exported from the DNA storage compartment (i.e., the nucleus) to various locations within the cell’s cytoplasm. At these sites the mRNA is translated to proteins. How do the various mRNA molecules get to the proper location? Are there any elements within the mRNA that dictate where to go? Due to the finicky nature of RNA, it has been difficult to answer these questions, but I’m trying.

So what is this all good for? Well, one way to answer would be a recent post of mine on technology. To state the idea breifly, humans are inept at creating new technologies from scratch. Technology here could be fusion power, a new drug or a vaccine. Often we need serendipitous findings to help spark the creation of new technology. This is why the government invests heavily in basic research. RNA interference (or RNAi), which can be used to inactivate genes and may help treat many diseases, was discovered by a researcher working with flower color in petunias.

A second answer that I can give you is this – if understanding cancer, Alzheimer’s or any other ailment, is like understanding a novel, then basic research is like learning the alphabet. Right now we have great treatments for AIDS and certain cancers, but we know very little about how it all works. That’s where basic research fills in the holes. When we finally know our abcs, then we will be better able to address all these other issues.

3. Would you say you live and breathe science or are you more of a 9-to-5′er?

Definitely the former. Life is incredible. There is so much to learn and discover.

4. You recently said that scientists will never have the solutions to all of our problems (which I wholeheartedly agree with). Could you explain that further? Are you postulating something that is beyond the scientific method, human experience, or perhaps the supernatural?

Solving problems invariably involves coming up with the appropriate technology. In turn, technology is, in a sense, the application of scientifically derived ideas. It is not always obvious how to transfer our scientific knowledge into a practical application. For example, we understand nuclear fusion, but we don’t have fusion power plants. In other words, we may understand how it works, but we don’t yet know how to make it work.

And so the question then becomes how do we come up with new technology? It’s very hard. We know a lot, but we’re missing some piece of the puzzle. And so we stumble in the dark. Then one day, by luck, someone comes upon some weird observation. This leads to new insight and the final piece of the puzzle. And so we have better ideas, better models and better tools. But we may never stumble upon the remaining piece. Or worse, there may not be any piece of the puzzle to stumble on, i.e., the particular technology is impossible. In that case we will never know whether we looked hard enough for that last piece. In some cases we know of the theoretical answer to our technological deficiency, but given the current resources, it is impractical.

If you look at the technology we thought we would develop in the past, like cheap interplanetary travel, much of it we just haven’t done. Instead we came up with technology that was beyond our imagination. Who would have thought of the internet 100 years ago? Or plastic? Or the human genome project? So any single technology is not inevitable, but not to worry, we’ll probably be spinning out lots of cool things that no one has even conceived of yet.

The scientific method is a tool, but no tool is perfect. Our limitations are not due to a supernatural world or human specific limitations, but to the fact that all tools and methodologies have limitations. Will science ever explain consciousness? Happiness? Well not only is science a tool but our ideas of consciousness and happiness are tools as well. We use these ideas to make sense of the world, but as soon as we probe the details of any of these ideas, the whole house of cards falls down. We need tools. This is how we solve our problems. But all tools are flawed. It’s a catch-22.

5. The genome revolution is upon us. How do you plan to take advantage of it?

The genome is an immense resource to the life-science community. Human geneticists have had a field day with it. They’ve already used it to piece together various aspects of our history, such as human migrations and our evolution, such as how we diverged from chimps and other apes. For molecular geneticists, molecular biologists and cell biologists, it has become an important tool. Now instead of fishing for a gene you can look it up. If we want to investigate how a certain RNA behaves, we can now isolate the gene that produces the mRNA all thanks to the human genome project. We can screen thousands of genes to see if they all share an RNA element that may alter the distribution of the mRNA, and we can compare the sequences of genes from different species to determine what RNA elements are conserved and thus play a biologically important role. The human genome is just the beginning, the real work will be figuring how the proteins collaborate to produce a living, adaptable organism.

Thanks, Alex. Dedicated scientists like you have a lot of discoveries and hard work to look forward to. Have fun and I hope you’ll keep sharing your thoughts and findings with the rest of us!