Made it!

Well, I am here in Manchester NH anyway. Still at the airport. An hour away from my final destination. I misread the bus schedule, and turns out I won't be able to catch the bus until 1:30, not 10:30, like I thought (sunday, duh). boohoo. So, at least they are progressive enough to have free wireless at the airport. I am always amazed at the larger airports charging for internet, yet small airports always seem to have it for free. So, I am going to work on my talk for a while. I finished watching a movie, and thought I'd update the blog, just in case anyone is actually paying attention :)

More from the meeting soon.


Meeting time

I'll be heading to a Gordon Conference next week. Specifically, the Cellular & molecular fungal biology conference. I have to give a talk, so will be occupied with that, and not so much blogging. But I'll try to summarize some of the cool work if I can.


Yeast are smarter than people

A recent post on a great site, Panda's Thumb, summarizes a recent article on de novo origination of a gene. What does this mean? de novo is latin for "from new", and its usage is wide, and can mean different things. It can mean "newly arisen function," and might also be referred to as ab initio, or "from the beginning." Anyway, the paper basically shows how brewer's yeast made a brand new gene from a set of nucleotides.


The planet as a petri dish

An interesting, if rather long, article points out that humans may well be over carrying capacity of the planet. I spend a lot of time working with microbes on petri plates, so I have little difficulty in seeing the analogy. It contains a quote from one of my favorite people, R. Buckminster Fuller, "It will be a race to either paradise or oblivion, right to the last moment." Think about how we run our lives as individuals. Rarely do we consider the long term consequences of our actions. Our evolutionary programing tells us to get as much as we can, reproduce as much as possible, and die. We've gotten pretty good at the first 2, and seem very hesitant about the last part. We will hang on as long as possible, the thought of death is frightening.

Believe it or not, I am an optimist. I like to believe better of humanity. I want to think that we are better than this modern world we've created/been born into. I hope the best we can do is yet to come. I don't want to think that it is Walmart, Macdonald's and Wii.

Consider the fact that a gallon of gas will take you, several people, and your gear, 20-30 miles. Do you think you could pay 1 person 4 bucks to do the same job? The reality is we've been able to overshoot our planet's carrying capacity by a lot because we've had "oil slaves" to do the work for 100 years. What will happen when that is gone? Will (can??) we be proactive? Or will it be chaos for many years, until the human population is down to a few million again?


Sex and the Red Queen

There are benefits of sexual reproduction. In 1932, Muller along with Fisher (1930) proposed that sex might purge deleterious mutations, and increase fitness over time. The idea was further expanded upon by Kondrashov (1988). This process has been shown in a homothallic Ascomycete, Aspergillus nidulans, where sexual and asexual lineages have very low level of genetic differences (Bruggeman et al. 2003). Mutations accumulate in both sexual and asexual lineages, but the sexual lineage suffers less fitness decrease over time grown under the same conditions. Another benefit of sex is thought to arise from the evolutionary arms race with competitors, pathogens and predators. This idea was originally proposed by Leigh van Valen (1973) and termed the Red Queen hypothesis, after Lewis Carroll’s "Through the Looking Glass." The Red Queen says to Alice, “it takes all the running you can do to stay in the same place,” meaning in an evolutionary context that for each novel beneficial mutation a species acquires, a competitor or pathogen will acquire a mutation to counter it, and so on, ad infinitum. Sexual reproduction can bring together genetic material from two different sources with unique successful mutations. Recombination potentially leads to novel resistance to a pathogen in a rare individual. Work by Lively, Craddock and Vrijenhoek (1990) demonstrates that populations of Mexican poecillid fish can reproduce sexually and asexually. In pools where there is predominantly asexual reproduction, the fish suffer more infection by parasites. In pools where sexual reproduction is the dominant mode, the population switches between two main genotypes, providing a “moving target” to which the parasite continuously adapts. The sexual population has greater fitness overall, but cannot repopulate pools as rapidly, and hence the maintenance of asexuality. Sex is though to benefit organisms because it increases the rate at which selection can fix beneficial mutations within the population because recombination over time breaks linkage between genes (Maynard Smith 1958, 1993; Fisher 1937). The ability to tolerate or adapt to changing environments, pathogens, predators and competitors is necessary for a species to continue to exist.


Protein-protein networks are robust

The derivation of protein-protein interaction networks of Saccharomyces cerevisiae, C. elegans and Drosophila has recently become a popular method for understanding the biology of these organisms. Network analysis is most advanced in the budding yeast, S. cerevisiae. The network of S. cerevisiae was developed using empirical methods such as yeast two-hybrids (e.g. Ito et al. 2001), expression profiling, identification of proteins in complexes using mass spectrometry, and systematic gene disruptions (Hazbun and Fields 2001). All of these analyses have allowed yeast to be the leading system for the study of protein networks. These networks have been found to be scale-free (Han et al. 2004). Scale-free networks are organized into a system of “hubs” and “spokes” where a few nodes (hubs) have more than five interacting partners, while most nodes (spokes) have five or fewer partners. Disruption of the hubs will cause much greater network perturbation than disruption of a spoke (Han et al. 2004). Therefore, disruption of a random node (protein) is unlikely to cause a serious disruption to function of the overall network (Han et al. 2004). This is one main argument for the ability of organisms to evolve. The protein network is robust, and the organism can still function in spite of mutations.


"we begin life as little scientists"

A really great article in the new yorker, that explains so well how science has affected my life. I came to science "late in life" after dropping out of college, after becoming incredibly disillusioned with life in the modern age. OK, I started reading Kierkegaard in my Norwegian lit class, and it just made me stop and think for about 2 years. That and I realized I didn't really want to be a lawyer, a major in Norwegian wasn't going to get me anywhere, and I was over my head in debt. Amazingly enough, I couldn't work 2 full time jobs, and maintain a 4.0, and live on my own at the same time. The pressure broke me.

Anyway, one morning I was sitting in my apartment in Billings, Montana; pondering what I really loved, what I was passionate about. I loved working in the garden. I loved plants. I loved soil. I loved going for walks, I loved reading and learning about all wonderful creatures on the planet. I realized/remembered/rekindled my love for genetics, ecology and evolution. I decided to move to Missoula that day, and return to school at the University of Montana, where I completed my BA and my MS. Best decision I ever made.


Host resistence to fungal pathogens

The basis of mammalian host resistance to fungal pathogens is relatively under studied. But what is the best model system for studying fungal disease? Many fungi are not host specific, that is, they have the ability to be virulent in many different hosts. Experiments can not be done in vivo in humans, but can they be done on human cell lines. Is a mouse model appropriate for understanding general mammalian immunity? Because mouse studies can be extremely expensive and a regulatory time suck, perhaps other models may be appropriate for understanding virulence in fungi (Casadevall 2005).
Recent work with C. neoformans shows that interactions with other soil organisms can be informative in screening virulence factors (Mylonakis et al. 2002). Further work in this system has revealed a specific gene required for pathogenicity in mice (Tang, et al. 2005). Other systems such as Aspergillus flavus and Candida albicans with the wax moth have also been described and show promise (Brennan et al. 2002; St. Leger et al. 2000). Another tool that is also being used to identify virulence factors in fungi is genome sequencing. Currently, several fungi are sequenced, or in the pipeline. Annotation has proven more difficult than originally thought, so the completeness of the data is limited as of now, and makes searching for "pathogenicity genes" using bioinformatic tools complicated and cumbersome.
The basis of host immunity to fungi is understood at a certain level. When mice without CD4+ lymphocytes are vaccinated with an attenuated Blastomyces dermatitidis and Histoplasma capsulatum vaccine, CD8+ T cells can induce and maintain protective immunity (W├╝thrich et al. 2003). Vaccine mediated protection was accompanied by reduced inflammation and fungal burden in the lung. In experiments with mice lacking both CD4+ and CD8+ T lymphocytes, the mice were not able to control the fungal burden very effectively with vaccination, but did show some resistance. Hence, the possibility that antibodies and/or B cells, in addition to other cell types, such as dendritic or NK cells, may play a role in the development of antifungal immunity, and has implications for vaccine development. The main result of this study is that even in the absence of CD4+ T cells, such as in AIDS patients, some immunity to fungal infections was obtained.