Questions for Van Gooch

Learn more about my research In January 2009, Van Gooch answered visitors questions about biology.

Your Comments, Thoughts, Questions, Ideas

Anonymous's picture
Anonymous says:

Do Circadian rhythms work the same in all people?

posted on Fri, 01/23/2009 - 4:25pm
Van Gooch's picture
Van Gooch says:

I do not claim to be an expert on circadian rhythms of the human, but the short answer to your question about variations in circadian rhythms in humans is: we don't know, yes, and no. The "we do not know" part involves the fact that understanding circadian rhythms is ongoing research. Doing any scientifically controlled experiments on humans is awkward, but trying to study circadian rhythms, which takes weeks of experimentation, is even more difficult. Hence, much of what we learn is from model organisms such as rats, fruit flies and the mold Neurospora. One characteristic of circadian rhythms is that they are typically innate and persist in constant environmental conditions; however, the period is usually not exactly 24 hours but some value that is about 24 hours, dependent upon the organism ("cica-" means about and "-dian" means a day). When humans are put into constant conditions, many physiological processes continue to cycle daily, usually with a period of about 25 hours rather than 24 hours. Indeed that period can vary from individual to individual. The concept that there are "morning people" and "evening people" is not refuted by circadian researchers. An interesting recent publication relevant to this question reported a genetic variation in a family line such that those members tend to rise very early and they have very short rhythms in constant conditions. The variation was found to be a single nucleotide in a gene known as the per2 gene. The per gene (short for period gene) was first discovered as central to the control of circadian rhythms in fruit flies. Subsequently, forms of the per gene have been found in a variety of animals, and humans have a form called per2. We also know that variations among humans may not necessarily be due to the clock mechanism itself but more related to how the clock gets reset. Since circadian rhythms typically do not run exactly 24 hours, it is important that there be a mechanism to reset the internal "clock" to the Earth’s natural sunrise/sunset cycle. Light is normally a strong resetting agent. Using strong lights at the right time of the day (light therapy) has been successful in treating some patients who have problems maintaining their daily cycle. Although verifiable differences in human circadian rhythms can sometimes be attributed to genetics and physiology, in reality most of the variations we see are probably a result of us being human. As humans, we have distanced ourselves from natural daily cycles by self-controlling light and temperature. Our social patterns and work schedules often dictate our daily patterns, and our common use of sleep altering drugs such as caffeine, alcohol, energy drinks, sleeping pills also affect our daily cycles.

posted on Tue, 01/27/2009 - 5:47pm
Joe's picture
Joe says:

What inspired you to pursue a career in biology?

posted on Fri, 01/23/2009 - 4:26pm
Van Gooch's picture
Van Gooch says:

As a kid growing up in the suburbs of the Bay Area in California, I would collect snakes, lizards, frogs, salamanders, butterflies, etc. The whole concept of life and nature fascinates me. There was no question that when I went to college I would major in Biology, even though I got better grades in Math and Physics. I continued on to earn a Ph.D. for no other reason than curiosity and wanting to learn more. In trying to understand how life works, it became clear that I needed to learn about cells, molecules and the chemistry of life. Becoming a professor was ideal because I could continue the learning process. Despite all of my education, there is no doubt one of the best ways to learn is to teach. Life continues to fascinate me. I am in awe of the diversity of life, from the organisms existing in the rocks of Antarctica to the ornate birds of the tropics. I am also continually amazed by the unity of life, for example, that all organisms have the same genetic code and that bacteria and the eyes of humans both contain rhodopsin molecules, which help them sense light.

posted on Tue, 01/27/2009 - 5:49pm
Rebecca's picture
Rebecca says:

How do you build a gene from scratch? Did you use anything from the original firefly gene? Why do you think it didn't light up properly?

posted on Fri, 01/23/2009 - 5:21pm
Van Gooch's picture
Van Gooch says:

DNA is a long sequence of nucleotides and there are four different nucleotides (A=> adenine, G=> guanine, C=> Cytosine, and T=> thymine), A sequence of nucleotides (e.g. AGGTCAGTT) can be ordered by internet from a biotech firm and the DNA sequence can be on my lab bench the next day. When I did this in 2004, the maximum size was around 40 nucleotides and we then put the pieces together, but today you can order the whole gene. You use nothing from the original firefly gene, all you need is the desired sequence. The sequence of many genes is readily available from a few giant databases to which scientists from all over the world contribute. So we simply downloaded the sequence, made the modifications we wanted, ordered the 40 nucleotide pieces and put the pieces together. Polymerase chain reaction (PCR) is a technique used in labs to make copies of DNA and was an important part in putting the pieces together and making enough of the gene to actually use. Replicating DNA by using PCR uses the enzyme that cells use to replicate DNA (DNA polymerase) and the individual A, G, C, and T nucleotides. It is a little more complicated than that, but not much.
So what modifications were needed to make the firefly luciferase gene work well in a mold? DNA codes for proteins and proteins are made up of a sequence of 20 different amino acids (for example the luciferase gene codes for the luciferase enzyme which is 550 amino acids long). A sequence of three nucleotides (codon) tells the cell which amino acid to use. There are 64 ways A, G, C, and T can put into three letter sequences but there are only 20 amino acids that are needed. It turns out that different codons can code for the same amino acid. For example TTT and TTC both code for the amino acid phenylalanine in any organism on planet Earth. However, we are now learning that there are preferences among organisms (a phenomenon known as codon bias) and we know that mold prefers TTC while fireflies prefer TTT even though both code for phenylalanine. Firefly DNA has all the wrong bias for mold and the mold is very slow at translating firefly genes. We changed all of those codons in the firefly luciferase gene to favor the preference of mold, and now the mold very easily translates the optimized luciferase gene and the mold glows like gangbusters. The end firefly luciferase protein is exactly the same, but 26% of the nucleotides were changed!

posted on Wed, 01/28/2009 - 12:09pm
Anonymous's picture
Anonymous says:

How did you come up with the idea to do this? What inspired you to pursue this line of research?

posted on Tue, 02/03/2009 - 3:00pm
Van Gooch's picture
Van Gooch says:

Curiosity. The idea of a daily clock inside a single cell makes me want to understand how is this possible. Using reporter genes to monitor what a particular gene is doing in a cell has been a popular and powerful tool in recent years. A reporter gene is simply a gene that when it is put into an organism it has an activity that can be easily monitored and reports the activity of some other gene. Luciferase has been one of the more highly used reporter genes.

posted on Thu, 02/05/2009 - 12:55pm
Anonymous's picture
Anonymous says:

Do animals that live near the poles still have circadian rythms? Does the all day sun or all day night have an impact?

posted on Tue, 02/03/2009 - 3:02pm
Van Gooch's picture
Van Gooch says:

An important thing to remember is that circadian rhythms per se is not the goal for organisms. The goal is to appropriately PREDICT times of the day such as sunrise and sunset so that the organism is prepared for this important event of the day. Day versus night are two very different ecological worlds and most organisms are far better adapted to one versus the other. It is important for the mouse to be in its hole BEFORE the sun rises so that the hawk doesn’t see him and it is important that a plant’s photosynthetic biochemistry to be in place BEFORE the sun rises so that it maximizes the daylight to come. Organisms also use their internal circadian rhythms to measure day and night length and thus determine season which, in turn, controls such things as breeding patterns. So it is obviously important for organisms away from the poles to have this strong predictive ability.
Now, back to your question. At the poles, some of the year the sun still rises and sets in somewhat of a normal fashion making the internal clock useful. Even at the solstices there is going to be a variation in intensity/spectral quality that may make it useful to have an internal clock. Unfortunately there has not been a lot of actual data collected on this interesting question. Reindeer and a bird (ptarmigan) have been show to lose their daily activity rhythm in the summer and winter but internal clocking mechanisms may still exist. Somewhat related, it has been commonly observed in the laboratory that under constant light that circadian rhythms often disappear. Also somewhat related, is a study done on beaver in the winter in its den. It was found that the beaver’s rhythm persisted, but it “free ran” at a period of around 27 hours becoming desynchronized with the outside world.

posted on Thu, 02/05/2009 - 1:00pm
Anonymous's picture
Anonymous says:

Why did you choose fireflies? Wouldn't bio-illuminescent algea be a closer "relative" to pull the genes from? (I don't really know what I am talking about so the answer for this may be a "duh").

posted on Tue, 02/03/2009 - 3:04pm
Van Gooch's picture
Van Gooch says:

This is actually a really good question. Bioluminescence is quite common in the biological world and has evolved multiple times, thus yielding all kinds of different biochemical mechanisms available to molecular biologists. Firefly luciferase has been the most popular gene used in this respect, but bioluminescent systems from bacteria, algae, and jellyfish have also been used. Firefly luciferase has some advantages in that it is a single gene that makes a single protein, that there is a substantial amount of literature about it, and its substrate (firefly luciferin) is relatively stable and accessible. But your question also asks if the codon bias in one of these other systems would be more favorable to Neurospora. The answer is I really don’t know and this is something I probably should have pursued a bit more before changing the firefly luciferase gene. I do know that the jellyfish system is also not very favorable to mold.

posted on Thu, 02/05/2009 - 1:01pm
Anonymous's picture
Anonymous says:

So, this isn't totally in line with your research, but perhaps you have a theory about why there seem to be fewer fireflies around these days?

posted on Sun, 02/08/2009 - 7:42pm
Van Gooch's picture
Van Gooch says:

Actually it is sort of on my lines since I study biological cycles. Besides daily cycles, it is common for organisms, such as insects, to undergo dramatic population cycles. Have you noticed how some years there are a lot of elm beetles, another year a lot of lady bugs, and another year a lot of grasshoppers. Fireflies also probably undergo dramatic cycles depending upon weather and prey. There is little research money to study fireflies despite the fact that they are fun to watch, Thus, population studies and effects of the environment on them are nearly nonexistent.

posted on Sat, 02/14/2009 - 2:31pm
Anonymous's picture
Anonymous says:

Why do animals like fireflies light up?

posted on Sun, 02/08/2009 - 7:44pm
Van Gooch's picture
Van Gooch says:

Bioluminescence has evolved independently several times for several reasons. As is true of the firefly, sex is often the natural selection force. Fireflies flash at night to attract a mate. In some parts of the world where different species of fireflies coexist in the same location, the flashing pattern not only signals the presence of a mate but also a mate of the right species.

Some animals light up as a protection. Some creatures in the ocean give off a cloud of bioluminescence to distract their prey. Flashlight fish have a light organ that they can blink on and off and then dart away; their prey gets a big mouth of water. Some fish give off light on the underside to exactly match the light coming from above so that predators below can’t see them.

The angler fish has a bioluminescent organ that hangs in front of its mouth that attracts prey. A little fishy comes up to check out the light and ends up as supper for the angler fish.

posted on Sat, 02/14/2009 - 2:29pm
Anonymous's picture
Anonymous says:

What other areas of biology are you interested in?

posted on Sun, 02/08/2009 - 7:48pm
Van Gooch's picture
Van Gooch says:

All of it. Life is just so cool.

posted on Sat, 02/14/2009 - 2:32pm
Anonymous's picture
Anonymous says:

Do your students help with your research? How?

posted on Sun, 02/08/2009 - 7:48pm
Van Gooch's picture
Van Gooch says:

The Morris campus has strictly undergraduates and the number one goal here is teaching. But to be a good teacher one needs to stay active in research. I ALWAYS involve undergraduates in my research. The best way to learn is to do it. So involving students in research is an important form of teaching. And then, every once in awhile, we come up with some good results. I have had students do presentations all over the country and they have published with me in major scientific journals.

posted on Sat, 02/14/2009 - 2:32pm
Kyoko's picture
Kyoko says:

Does Biology relate to becoming a veteranairian in a major way? or is it just minor or not at all?

posted on Mon, 02/16/2009 - 2:51pm
Van Gooch's picture
Van Gooch says:

To be a veterinarian you have to understand the biology of the animals you are trying to treat. You have to know how the heart, lungs, kidneys etc. work. You need to understand the cellular and biochemical activities to give appropriate drugs. You need to understand how the nervous system works so you have a sense of the animal feels since they can’t talk. I would NEVER take Artimis, my cat, to a veterinarian who does not have a deep understanding of Biology. Indeed, to get into Vet School you must have a strong background in biology.

posted on Tue, 02/24/2009 - 2:23pm
Anonymous's picture
Anonymous says:

What's the next step in your research?

posted on Fri, 02/20/2009 - 5:44pm
Van Gooch's picture
Van Gooch says:

I am very interested in the effects of light on the clocking mechanism. Classically we have followed the daily formation of spores in Neurospora to monitor its rhythm. In constant light spores are formed constantly and because of this light effects have been poorly studied in this model organism. We believe this response to constant light may not be a stopping of the clock but rather a downstream effect of light directly on the biochemistry of spore formation. With the bioluminescent system we can measure the rhythm at the molecular level of the clocking mechanism itself under different lighting conditions (although we do have to turn off the light momentarily to make our bioluminescent measurements.).

posted on Tue, 02/24/2009 - 2:40pm
Anonymous's picture
Anonymous says:

Could an animal or bug be retrained to a different circadian rythm?

posted on Fri, 02/20/2009 - 5:44pm
Van Gooch's picture
Van Gooch says:

This is going to be another one of those Yes and No answers. First of all the answer not only applies to animals but also plants and single celled organisms. There is a common experiment that circadian rhythm biologists do called “entrainment”. For example we may give a repeated 14 hours of light and 14 hours of dark (14L:14D) cycle and see if the organism follows a 28 hour day. The answer is almost always yes. When you get to a certain point (e.g. try to force a 30 hour day or 16 hour day) the organism starts to ignore the light dark cycle and just acts like the environment is non-changing and we say we have reached the limits of entrainment. When the organism is entrained, is it really “trained” to these new cycles when we go back to normal or constant conditions and the answer is NO. The organism will always return to its natural internal cycle.
Students often ask me the following question, which might be the impetus of your question. “If I force myself to only sleep 5 hours per night, will my body learn this so that I effectively get more awake hours per day?” Research on this subject in humans gives a clear and strong answer of NO. Certainly, as humans, we can force ourselves into longer awake periods than our body dictates, but we are simply more sleep deprived during our awakening hours and less effective. And the action never changes one’s inherent cycle.

posted on Tue, 02/24/2009 - 2:26pm
Aquinas's picture
Aquinas says:

Why do so many eminent biologists grow beards?

posted on Mon, 02/23/2009 - 12:58pm
Van Gooch's picture
Van Gooch says:

Well my first response would be let’s do the research and see if the premise is true. And we would have to put the emphasis either on “eminent”, “biologists”, or “scientists”. But let’s, for the fun of it, assume that scientists tend to grow beards more than the general public and why that might be so. I think scientists might be a little bit more maverick and free-thinking than the general public and this might be related. Maybe it is simply the stereotypic image and the scientist wants to live up to that image.
What about my beard? While I was a graduate student at UC Berkley, I got really sick with bronchitis and was literally in bed for two weeks (no shaving). My girlfriend (now my wife) said she really liked the beard and that I should not shave it off. I have now had the beard for 34 years! The thing I like most is the 10 minutes it saves me every morning not to have to deal with putting sharp blades on my face.

posted on Tue, 02/24/2009 - 2:27pm
JoeB's picture
JoeB says:

Came over from Pharyngula, and very much enjoyed reading your replies. The luciferase transfers are fascinating.
Your statement about the sun rising and setting on some days in polar regions--only true beyond the arctic/antarctic circles, right? Inside the circles, the sun swings around at nearly the same elevation above (or below) the horizon for weeks at a time.

posted on Mon, 02/23/2009 - 4:44pm
Van Gooch's picture
Van Gooch says:

True

posted on Tue, 02/24/2009 - 2:28pm
Stagyar zil Doggo's picture
Stagyar zil Doggo says:

Counters:
Discussions of Circadian clocks usually refer to a clock period of around 24 hours. Is this the basic period of the timing device (molecular clock)? Or does the Clock consist of a device with a much smaller period coupled with a counter of some sort? Are counters involved in estimating periods of multiple day length (e.g. menstruation cycles)?
Humans at least appear to have abilities to estimate (if crudely) much smaller periods of time - an hour, a minute or even a second. What is the source of these abilities? From whence does the exquisite timing ability of expert musicians arise, for example?

posted on Tue, 02/24/2009 - 4:02am
Van Gooch's picture
Van Gooch says:

Lots of good questions here that have been previously asked by researchers but we have no clear answers. We know quite a bit about the molecular mechanism of circadian rhythms and the results tend to argue against counters; rather it is just slow biochemical and genetic feedback mechanisms. An interesting classic study in fruit flies involves mutations of the per gene, known to be directly involved in the circadian timing mechanism of fruit fly daily cycles. Mutation of the per gene changes the fruit flies daily cycle but it also affects the frequency of their high pitched mating song! Not a lot of research has been done on the role of the per protein in the mating song but it is likely a difference in kinetics rather than counting.
Clearly humans can count using their daily cycle. People experimentally isolated in caves have a good idea of how many days they have been their by counting their daily cycles (although they usually underestimate the days because the human free running period is around 25 days.) Probably most animals have a similar concept. (The menstruation cycle is clearly not an example of this, but merely depends on hormonal feedback loops and ovarian and endometrial developmental times.)
How do we and animals count short time periods and is this related to the circadian cycle? I think the answer is yes, but I am going to ask my friend Dr Koukarri who I think has a better answer to this question. I will get back to you. Dr. Koukkari and Dr Sothern of the University of Minnesota have written a very good book entitled “Introducing Biological Rhythms

posted on Tue, 02/24/2009 - 2:30pm
Stagyar zil Doggo's picture
Stagyar zil Doggo says:

Many thanks for your response, Prof. Gooch.

Mutation of the per gene changes the fruit flies daily cycle but it also affects the frequency of their high pitched mating song!

That is quite fascinating. It suggests that the per gene also participates in determining the size, mass or stiffness of the (macroscopic) part of the body that produces the mating song.

(although they usually underestimate the days because the human free running period is around 25 days.)

... perhaps you mean 25 hours?

(The menstruation cycle is clearly not an example of this, but merely depends on hormonal feedback loops and ovarian and endometrial developmental times.)

But given that hormonal secretions, as well as ovarian and endometrial development times probably are regulated by the basic circadian clock, isn't this probably just an elaborate counter? I mean would the menstrual cycle have the same duration in a person with a mutation that halves or doubles the period of their circadian clock?

I think the answer is yes, but I am going to ask my friend Dr Koukarri who I think has a better answer to this question.

I'm looking forward to Dr. Koukarri's response and I appreciate your offer to ask him.

Periodic signals of widely varying frequencies occur in almost every kind of physical system, and many of these can be easily forced into limit cycles. Given this, I find it strange that all of biology uses only a single type of fairly inaccurate molecular-genetic timing system operating at essentially the same frequency. How come there are no biological clocks that keep time using the frequency of vibration of a bone, or the time taken to squeeze a volume of fluid through an orifice or a pair of neurons which excite each other sequentially, or any of a hundred other possible ways to keep time?

Of course, I'm guessing that such other types of timing devices do exist, and that they're so far undiscovered/not widely known/not known just to me. :-)

best regards,
Stagyar zil Doggo.

posted on Fri, 02/27/2009 - 2:38pm
allibyrd's picture
allibyrd says:

If circadian rhythms are triggered by light, wouldn't the glow from the firefly gene turn off any fungal reproduction of the sort you wrote about? Or is there not enough UV light in such glow to trick the fungus into thinking it's daytime. ;)

Thanks for your response,
Allison

posted on Tue, 02/24/2009 - 9:39am
Van Gooch's picture
Van Gooch says:

A very insightful question and one that has literally kept me up at nights. So when we developed this system, there was a major worry that the light generated would affect the clock. The light intensity generated by the bioluminescence is very very low, so our hope was that it would have minimal effect. Our test would be if the rhythm continued in a normal fashion as it bioluminesced, and it does. But it is still a nagging concern. Even though the intensity is very low it might actually be very strong right on the surface of the luciferase molecule where the reaction occurs, and the molecule that detects light for the rhythm might be right next to the luciferase molecule. Our best answer for the moment is that it works, but we need to not forget this concern.
You are right to point out that only certain wavelengths (colors) affect circadian rhythms. Neurospora circadian rhythms are mostly affected by blue light (and none by red) and the more yellow spectrum of firefly luminescence does overlap with the sensitive region of Neurospora. We were just lucky (which is part of science) that it doesn’t seem to have an effect.

posted on Tue, 02/24/2009 - 2:32pm
Anonymous's picture
Anonymous says:

I know that biology often cooperates with fields like chemistry and medicine. But how does biology interact with less-obvious fields like Astronomy and Physics?

posted on Fri, 02/27/2009 - 9:50am
Anonymous's picture
Anonymous says:

Do Circadian rythems work the same in all people?

posted on Sat, 02/28/2009 - 5:49pm