Archive for: January, 2009

Research Crossroads

Jan 30 2009 Published by under Uncategorized

I know, I know, 5 months in is a little early for any kind of crossroads, but I had a bit of an epiphany yesterday that may shape the next 6 months. The main project I want to pursue has some fairly high up-front cost - at least for my field. Because of that, I have been in a holding pattern of that project until I get grant funding for it. Yesterday I realized that I could do a small-scale test project for considerably less than what the full project would cost and now I am debating what to do.

The reason it might be worth jumping the gun and producing these data before getting a grant is because this project falls under the high risk/high reward category, that is probably unlikely to get funded without some decent evidence that there will be the results that I think there will. When I sent the grant in back in January, we had made progress, but hadn't made the final leap because of the cost. I have no idea, of course, whether the progress we made will be enough to convince the reviewers to suggest funding the project, but if it gets turned down again we won't have much more evidence in hand for the next round. From that perspective, it seems like a huge gamble NOT to spend the money.

The drawback is that it all needs to come from my start-up. Not only that, but if I want to get it done before the July round of grant applications (assuming the grant doesn't get funded this round) I will need to figure out if the Dean will let me borrow against my start-up money for next year, early. When I negotiated my start-up, I got the vast majority in the first year so I could buy equipment and get things running. I have pretty much outfitted the lab at this point and still have about $25K left for this year. Since the fiscal turns over June 30, that should give me plenty to get through this year. BUT, if I were to go for broke and try and pull this off, I will need to pay about $10K to one company and $15K to another. Obviously that would leave me with nothing to use for the other projects going on in the lab and the consumables to keep things running.

I have $75K of start-up available in year 2 (starting July 1), with nearly that much coming in year 3, so time is a bigger factor than money in the grand scheme of things. I have no problem spending the money (that's why it's there), but I don't what to handicap the lab for a few months either. The way I see it, I have three options:

1) Hold tight and see what happens with the grant. I am not a conservative person and this option bothers me. If the grant doesn't get funded, I will have very little to add in the next round, which is only treading water.

2) Spend the $10K to complete the first step of the project and have at least made that progress in the even that the grant does not get funded in this round. Even if it does, I would have to spend this money anyway, but from the grant rather than start-up. I could live with this option because it shows that we can do what we claim, but it will not provide any evidence of the eventual outcome.

3) Squeeze the Dean for some of next year's money and produce the data. This option is the scariest in the short term, because the lab finances will be dodgy until summer, but it would provide enough data to push the grant over the top, for sure. These data could also be folded into the larger data set once we had the funding for the whole project. Of course, this is predicated on squeezing blood from a stone in this financial climate because the Dean may not even be able to provide any money for me to move forward.

4 responses so far

Motivational metric

Jan 29 2009 Published by under Uncategorized

There have been a number of metrics being devised since Drug Monkey revived the establish your own scientific eponym meme. I bounced a few around in my head, but was embroiled in grant-related issues at the time and never got around to putting any down. In the past couple of days I have spent a lot of time tinkering with the structure of my course and putting some lectures together. As I am putting the finishing touches on some of them, it's been pretty clear that I have created a motivation metric, without having to think about it. It's simple and direct. The motivation I have to get parts of a lecture done are inversely proportional to the amount of challenge I find in the subject. Therefore, when I am teaching something a little out of my comfort zone, I focus on getting the slides together in a very organized way to get my point across clearly. If the topic is something I am very comfortable with, I leave the slides blank while I do things like blog about why I'm not actually doing the work I need to finish.

2 responses so far

For the love of salt

Jan 29 2009 Published by under Uncategorized

Our entire area has been turned into a giant skating rink by Mother Nature's latest hijinx and in its infinite wisdom, Employment University decided to plow everything in such a way so as to leave a half inch of ice on everything. Well, since they did not plow the sidewalks at all, there are 2 inches of ice on those, but who's counting? When I drove in this morning, students were walking in all the roads around campus because the probability of being crushed by a sliding car was apparently less than that of cracking one's skull on the skate-walks. With ice and students everywhere, navigating to my parking lot had to be done with surgical precision. Luckily, I have been conditioned to walking on ice because both PhD City and Postdoc City were frozen wonderlands for much of the year. In addition, due to the construction on the new building next door, the university plows have decided that they should not get within 200m of anything that resembles a construction fence, so icy walkways have been the norm around the current building all winter.

Figure 1. PLS's walk from parking lot to building.

On might think that salt and sand might be a simple way to combat the problems associated with an ice coating, but Employment University believes in green energy and prefers to let the sun do that job, no matter how long it takes and how many shattered pelvises must be endured. While I have to admit that the jerk in me found comedic value in watching three students dramatically yard-sale on my short walk in (with no apparent injury, save for their egos), I do wonder who makes cost-saving decisions like not using salt and how they factor in the injuries of their clients (students) and employees into how much money they are saving.

4 responses so far

Defying Big Blue

Jan 28 2009 Published by under Uncategorized

I have a confession. I am a Mac guy. From the very early days of home computers I have pretty much always had a Mac, either at school/work, home or both. My lab is entirely Mac and I was never forced into using a PC throughout grad school or in my postdoc, since those labs ran Macs as well. I can use a PC with no problem, but the times I have owned them make me pine for my Mac. There really is no comparison, especially when you consider the rate of performance decline as the machines get older. You can run a Mac for years on end, but a PC is basically a doorstop in 5 years or less.

Despite my personal bias, I have always used Microsoft products because there was no real alternative. Remember in the early 90s cursing because someone sent you a WordPerfect document that couldn't be opened in any other software? I do and I didn't want to be that guy. The good people at Apple also realized this and when they made their Office equivalent, they went to great lengths to ensure that people could import ppt documents with ease and export presentations in ppt format. Despite this, I hesitated making the switch because of the "unreadable file" prospect that looms over any potential speaker at a conference. I wasn't going to make two presentations (one in PowerPoint and one in Keynote) just to avoid this, so I continued using PowerPoint.

The difference now is that I have a class to put together and I am using my own laptop. There is virtually no way that I might face any compatibility issues here, so I think I am going to create my lectures for class this semester in Keynote. But before I do, I thought I would solicit any advice on potential drawbacks of moving to Keynote. I don't that Mac has the answer for everything, so if I am about to run into a massive pitfall by switching (for class, not international presentations), better to know that now.

5 responses so far

NFtOS 2. Alveolates: Nature's genomic mind-fuck

Jan 27 2009 Published by under Uncategorized

Today I thought I would get into a bit about the bizarre beasts in the alveolate group (Fig. 1). Chances are, the term "alveolates" means nothing to you unless you care about the classification of eukaryotes on a broad scale. However, you will certainly be familiar with some of the organisms that are within this group, which includes ciliates (e.g. Tetrahymena), apicomplexan parasites (e.g. Plasmodium, Toxoplasm), dinoflagellates (responsible for red tides) and a couple of other odds and ends that are not important for today's topic but have features heavily in recent debates over the evolutionary history of the lineages.

Figure 1. The major groups of organisms that make up the Alveolata and their evolutionary relationships to one another. The branch leading to Chromera is dashed, indicating uncertainty of its exact affinity.

What is really interesting about this group of organisms is that the all seem to have something really strange going on with their genomic structure. Ciliates contain two nuclei within their single-celled selves, one of which functions as the germline nucleus (called the micronucleus - MIC) whereas the other is the somatic nucleus (macronucleus - MAC). The MAC is the transcriptionally active nucleus and is a highly-processed version of the "silent" MIC and can range between ~120 chromosomes large chromosomes to over 25 million, gene-sized chromosomes, depending on the ciliate. In all known cases, the MAC of daughter cells is produced in a complicated RNA interference-based process of comparison between the parental MAC and the MIC. The processing of genetic information in ciliates is a fascinating subject that science is only beginning to figure out.

Apicomplexans are another unusual group, but I've already discussed them a bit in the past. The moral of the story is that you shouldn't tease little algal cells because you never know when they'll evolve into parasites and cause millions of human deaths annually.

Finally, you have the dinoflagellates. Even though the Amoeba nucleus is the Godzilla of genomes (~670,000 Mb), some dinoflagellates could make a case that their nuclei are at least the Mothra of genomes. Gonyaulax, for instance, has an estimated nuclear size of 98,000 Mb - a mere 34x the size of the human genome. While this alone puts dinos in an unusual genomic category and pretty much ensures that it will be a while before we see a dino nuclear genome completed, it is their plastid (chloroplast) genomes that are truly messed up. Rather than having a single circular plastid genome containing all of the plastid-encoded genes, dinos have fractured their highly reduced plastid genomes into hundreds of plasmids, called minicircles. Only a few genes are individually encoded in multiple copies on these circles and a large proportion of the minicircles are non-coding, containing only the screwed up results of recombinations between different copies of genes. Each minicircle has a a core region, which presumably functions as the site of transcription. Clearly the system has evolved in response to some genomic pressure, but what the possible advantage is of having hundreds of divergent copies of a few genes and a large amount of junk being transcribed in your plastid is, remains a mystery.

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European ref letters

Jan 27 2009 Published by under Uncategorized

As much as I bitched about not getting any decent candidates with a week to go in my search for a PhD student, I did get a couple good applications in the end. I have asked for reference letters from the list provided by my top candidate and have been surprised by what I got back. I have two out of three in hand and the first was sent to me less than an hour after I inquired. What I received was a three sentence email paragraph basically stating that the candidate was highly recommended, but little else. I got the second letter last night as an attachment, but the first and last paragraph used the wrong pronoun to refer to the candidate, whereas the middle two used the correct one. Ummmm, okay... How am I supposed to take that? The two middle paragraphs are a total of four sentences and indicate a high regard for the candidate, but how highly can you think of someone if you don't even take the time to read over you letter for them? Can I trust that someone really puts their "full and unreserved support" behind someone when they use the wrong pronoun to refer to them in the same sentence?

The mitigating factor here is that the candidate is from Europe and I don't know much about what would be expected as a reference there and whether it would be different from what North Americans might write. An additional complication is the language barrier, so the reference writers may truncate their comments if they have to write them in a non-native language. Is there something I am missing or did the candidate just pick lazy reference writers?

7 responses so far

Less Neurotic than most

Jan 26 2009 Published by under Uncategorized

Because today was an absolute wash in terms of getting anything done, I took the blogger personality test that a few others have posted about. Basically I am the polar opposite of both River Tam and PiT, more along the lines of Arlenna, but less neurotic and less open to new ideas. What does it all mean? I have no sweet clue.
You scored 14 out of 50. This score is higher than 4.1% of people who have taken this test.

You scored 42 out of 50. This score is higher than 86.7% of people who have taken this test.

Openness to experience
You scored 42 out of 50. This score is higher than 52.9% of people who have taken this test.

You scored 43 out of 50. This score is higher than 90.3% of people who have taken this test.

You scored 44 out of 50. This score is higher than 89.7% of people who have taken this test.

2 responses so far

NFtOS 1:Are you a heterokaryon?

Jan 23 2009 Published by under Uncategorized

Today's question is whether all your genes are yours. It's a more complex question than it looks, but we have some history to deal with.

I think we can pretty much all agree that prokaryotic cells (bacteria and things without those pesky organelles) are more ancestral in the grand scheme of life than eukaryotic cells (with a nucleus, mitochondria and sometimes plastids). Based on that, we can probably agree that prokaryotes evolved earlier and were the earliest form of life as we know it on our planet. There's lots of data to back this up that I won't get into here, but you can search it out if you think I'm making shit up. The two big questions in the biology of organisms way back when, are 1) how did the first cells evolve, and 2) how did we get from prokaryotic cells roaming the Earth to the first eukaryotic cell? At the moment, we just don't know. There are lots of hypotheses out there, but in the current state of science the question of how the nucleus came to be and the origin of the genetic material that now inhabits this organelle are merely questions we can argue over. I happen to think we will someday be able to explain the phenomenon, but we're stuck at the moment.

An aside here. If you are reading this and thinking that the solution has anything to do with a divine being of any kind, it's time for us to part ways. Seriously. I'm sure there are blogs out there on fairies and imaginary friends you can talk to at night, but we're not having that conversation.

Though theories on the origin of the nucleus abound, we know considerably more about the origin of the other organelles in eukaryotic cells. It turns out the plastid (aka, chloroplast) evolution is a complex mess involving (probably) one instance where a cyanobacterium (photosynthetic bacterium) was engulfed by a eukaryotic cell, but never digested. Over time, the cyanobacterium and host cell learned to live together to their mutual benefit and, as often happens in these situations, the cyanobacterial symbiont became reduced over generations and time to the point where it became obligately bound to the host cell. Once this was established, eukaryotes spent the time between then and now swapping plastids around like lice in a daycare.

The case of mitochondria is very different. The mitochondrion became part of the eukaryotic cell in the same way the plastid did, but much earlier on. In the late 1980's it was thought that there were organisms that did not contain mitochondria and that they were the most primitive eukaryotes. Since then, it has been shown that the position of those organisms in the tree of life was an artifact and that eukaryotes don't entirely lose mitochondria. Ever. Mitochondria got in once and they got in early. So early that there is no evidence of any eukaryote that lived prior to mitochondria.

But here's the kicker folks. We think that the ancestor of mitochondria belonged to the group we know know as the alpha-proteobacteria. Current day alpha-proteobacteria have good sized genomes with a couple thousand genes to make the proteins they need and we have no reason to believe that the ancestral proto-mitochondrion needed fewer genes than current day ones. However, modern mitochondria have anywhere from 0 to less than 100. In fact, almost all animal mitochondrial genomes have only 13 protein coding genes, which is another reason my animals are really damn boring, but that's for another day. So, what happened to all those bacterial-turned-mitochondrial genes? If the genome came in with a few thousand and now has, in the case of animals, 13, where are the rest?

That question brings us back to the topic of the day. It turns out that while many of the "missing" genes have been ditched because they were no longer needed in the cell's new role as a mitochondrion, 13 proteins are not nearly enough to run the mitochondrion. Rather than make the proteins in the mitochondrion from it's own genes, it has out-sourced that job to the nucleus. The vast majority of genes that make mitochondrial proteins are encoded on the nuclear genome and the proteins find their way through a complex targeting pathway. But, what should be the interesting thing here is that these genes have all been transferred from a prokaryotic cell and incorporated into the eukaryotic nuclear genome. Many of these genes are identifiable in phylogenies based on the sequence affinity to prokaryotes that they have retained, but some have been part of the eukaryote for so long that they just blend in. Therefore, the typical eukaryotic genome is home to thousands of genes that have bacterial origins and many of which perform cellular functions unrelated to the mitochondrion because they have replaced the canonical copy or they have assumed a novel function in the cell. So, in addition to the recent estimate that humans carry more bacterial cells than human cells, we also carry a decent number of bacterial genes in our genomes.

One response so far

Easy screening

Jan 22 2009 Published by under Uncategorized

The college did what appeared a few weeks ago to be impossible. Our new building actually opened on schedule and classes have been held in there this week when the semester began. Since all of the classes that were formerly taught in our building have be moved to the new building, the halls here a very quiet. Large signs have been posted at the entrance to our building that scream in big red type "All classes for old building are now being held in new building. The one right behind you. Yes, turn around and walk" - or at least something like that.

Despite the big signs, the deserted halls and the fact that the classrooms are dark, locked AND have different numbers than the ones in the new building, there are still students walking the corridors with the vacant, lost look in their eyes. I have no idea how many times I have answered the question "Do you know where room xx is?" in the last couple of days. It's hard for me to answer these kids with a straight face, because they are essentially admitting that they ignored the building name and number on their schedule, the big red signs and are oblivious to the fact that there are no other students in this building. I should get every one of their names so I can screen them from anything I do in the future.

I teach my first class tomorrow (hence no sciencey post today) in the new building and the lab moves in less than two weeks! I would walk my equipment over there barefoot if it would get me in any sooner.

3 responses so far

New series: Notes From the Other Side

Jan 21 2009 Published by under Uncategorized

Considering I just started this blog in October, I would say that there might still be a whiff of that new blog smell around here. As a newcomer to this community I have learned a lot and gotten a good amount of useful feedback from those with more experience in matters of blogging, teaching, being a PI and everything that comes along with that. I appreciate the comments and they have actually changed the way I approach what I post here. My initial intention was to chronicle my experiences with the hope that they would inform those who are now in the position I was a year ago. While I still try and do that, I also now use this forum to draw on the experiences of those who are further along in this process than myself.

With the new semester upon us, I think it's a good time to add another aspect to the blog and that is to talk a bit more about actual science. As I have begun to explore some (I wish I had the time to read further than I do) of the other sciencey blogs out there I've realized that the research programs of bloggers roughly reflects research biases in the US - that is to say that a large sector of the community works in biomed-type fields and of those who do not, many still use model organisms (human, mouse, fruit fly, yeast, Arabidopsis, etc.) in their experiments. Though a lot of people don't reveal their field, I get the impression that nearly all of the bio-bloggers are working on organisms that would be household names (alright, maybe in a geeky house, but still). That puts me in a niche market, I suppose.

Over the next couple of weeks I'm going to try and put a few coherent posts together on some of the interesting things going on outside model organism world. My motivation for doing this actually came from a manuscript I recently reviewed for a high-impact journal. The authors actually wrote the line "We have shown that xx holds true for the entire spectrum of eukaryotic diversity, from humans to yeast". This kind of shit drives me crazy and is the equivalent of saying "Last summer I drove all across the US, from Maine to New Jersey", but I have seen similar statements in a grant and two seminars. I have no idea if the posts in this series will actually attract any readers, but if I can get just one person to realize that eukaryotic diversity hasn't been neatly classified as Animal, Plant or Fungus since the 1950s (or earlier) or that the organisms we can see out our window represent the minority of eukaryotes, then I will be happy. At the very least, it will save my grad students from having to listen to my crazed rants when I come across statements like the one above.

6 responses so far

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