Transcriptional Responses to the Environment
Karen Adelman, Ph.D.
I understand you've been doing some really groundbreaking research, and I have to tell you I'm not really sure what transcriptional responses to the environment group means. What do you do?
We do very basic research, trying to understand how it is that cells respond to stresses from their environment. Now, that can be an immune challenge or that can be an exposure to a toxicant. What's really important for cells that have these kind of exposures is that they can really rapidly find the information within this huge genome of DNA to turn the right genes on so that the cells can actually survive this kind of threat. And so what my group is interested in doing is really trying to figure out how the information is found quickly and how the gene response can be precise and rapid.Transcriptional Responses
Alright, so then tell me about the advances that you that found and how you understand this gene expression. Your advances have actually contributed to our understanding of the gene expression.
For a number of decades people were really trying to understand the stress response by studying one gene at a time. And, so what's really been great about the genomics revolution that's happened in the past decade or so is that now we can look at the whole genome and get a more comprehensive and kind of integrated picture. So, you know, you can think of it as for decades people were kind of walking around in their backyards with a flashlight and you could see wherever you were particularly looking, where you were pointing your flashlight. Genomics has really allowed us to kind of turn flood light on and to ask now over the whole of the genome, “What are the patterns that we can find and how is gene expression then coordinated?” And so some of the research that my lab has done has been asking, “How is it that genes that need to be turned on really rapidly during stress are found very quickly and efficiently by the cell?” We find that, in fact, what the cell does is basically what you would do; they bookmark these really important sites in the DNA so that instead of having to dig through this whole library of information, they already have proteins sitting there on these regions of the DNA to kind of tag them so that they can be found quickly.Advances in Gene Expression
How do they tag them? How does that work?
Well, in fact what they do is there is a particular group of proteins that's necessary for reading the information in the DNA and turning that into, eventually, proteins. So what the cells do is they just sit all that protein machinery on the DNA ready to go. So you can imagine it's like bringing everything that's necessary to the site and just saying, "Sit here until we pull the trigger," rather than when stress happens having to assemble this entire machinery on a particular portion of the genome.DNA Tagging using Proteins
So basically when the car's turned on, this is ready to go. With nobody behind to handle the stress?
Right. Everybody is in the car. You just need to turn the key in the ignition and you are ready to go because you are packed.Analogy for Transcription
In your studies you use what you call ChIP-chip and ChIP-seq technologies. What the heck is that and why did you choose them?
This is part of this whole genomics revolution which allows you instead of just looking at an individual gene or a handful of genes at a time to really be able to assess protein distribution across the whole genome. So if, for example, you are looking for where is the car is parked across the whole genome, if you are looking using these ChIP-chip or ChIP-seq techniques, you can access an entire human genome or mouse genome in a week's experiment.Sequencing Techniques, pt. 1
So both ChIP-chip and ChIP-seq, are they both different kinds of floodlights?
are incredibly powerful floodlights, and they use slightly different technologies...Sequencing Techniques, pt. 2
Is one better than the other one?
No, in fact, I think they give very different bits of information...Sequencing Techniques, pt. 3
Give me an example.
With ChIP-chip, you do not have the same kind of spatial resolution, but it's much better to compare between samples. So let's say you have a patient with a disease and a healthy individual and you want to compare where the car is sitting in the two different situations. ChIP-chip is better for doing this comparative analysis, because you can look at the two samples in the exact same experiment. Whereas ChIP-seq gives you a better idea of the position at which something is sitting but it's a much more difficult technique to use to do comparisons.Examples of Sequencing Techniques
Alright. So, looking more broadly, how does your work fit into the Institute's overall mission?
One of the things that's been really interesting in this study is that the genes where we find the car parked and the whole family ready to go tend to be the genes that are most important for responses to environmental stresses and toxicants. So we've really been doing a lot of work studying this kind of poising at developmental and immune responsive genes. We find that the car is ready to go on many, many genes that are really important for regulating the immune response and the innate immune response. And this is tying in very, very nicely into what others in the institute are working on trying to understand how individuals react differently to environmental stresses.Study Related to NIEHS Mission
We have just 10 seconds left. Anything else you'd like to add in terms of the potential for this type of research?
Well, no. I think that this genomic research is allowing us to assess very precisely what questions we need to ask in the future. For many years people asked, “How does the car find its target sequence on the DNA?” Now we know that's not the end of the story. What's really important is figuring out how you turn the key in the ignition and where you go from there.Future Research