Last night, I had a dream that I explained the concepts of homeostasis and allostasis to a room full of Midwestern tourists. 

That means something, right?

Just took a break from thesis proposal revisions to write that recommendation letter for my summer student. 

I have to say, I write a mean recommendation. He’d better get into whatever school his little heart desires. 

Too many ideas for good handwriting.

Too many ideas for good handwriting.

I’m having way too much fun making schematic diagrams with ChemBioDraw. It’s just like Photoshop, only I can understand it.
Cyclic nucleotide-gated ion channels for the win?

I’m having way too much fun making schematic diagrams with ChemBioDraw. It’s just like Photoshop, only I can understand it.

Cyclic nucleotide-gated ion channels for the win?

Friday night science.

Friday night science.

Hey Tumblr,

So last Friday, I gave a chalk talk about the biology of addiction and stress (and other science stuff) to a group of artists as part of my friend Maryam’s artlab series. 

ArtLab grew as a natural extension of Maryam’s role as manager of the mixed-media arts company, Our Ladies of South Fourth Street, which operates out of Brooklyn, and her work as a scientist and artist. I was honored to be invited to Our ladies’ home base to talk about my work and my views on science and art in what will hopefully be the first of a long list of discussions between scientists and artists of all types. It was a really great time. Enjoy this snippet of my talk. Forgive the nerdery.

D

(here’s a second clip of my talk for those who are interested; especially if you ever wanted to know why I got into addiction research)

Edit: ArtLab is on Facebook. Like it!

Svante Pääbo is giving a lecture at the Rockefeller next month! 

From the event description:

Dr. Pääbo’s laboratory develops techniques for extracting and analyzing DNA from Pleistocene fossil remains. They recently produced a draft genome sequence from Neanderthals, who lived in western Eurasia until becoming extinct around 30,000 years ago. They found that about 2.5 percent of the genomes of people living outside Africa derive from Neanderthals. Dr. Pääbo’s lab has also sequenced the genome of a finger bone from Denisova cave in southern Siberia. They show that it derives from a hitherto unknown group of hominins, which they call Denisovans. Approximately 4.8 percent of the genomes of people now living in Papua New Guinea and other parts of Melanesia derive from Denisovans. Together, these findings suggest a “leaky replacement” scenario of human origins in which anatomically modern humans emerged out of Africa and received some degree of gene flow from archaic human populations in Eurasia that they ultimately replaced.

The Neanderthal and Denisova genomes allow the identification of novel genomic features that appeared in present-day humans since their divergence from a common ancestor with their closest extinct relatives. Dr. Pääbo will describe a preliminary analysis of these features and illustrate how they can be functionally analyzed by the example of FOXP2, a gene involved in language and speech production.

Dr. Pääbo’s work is a really good example of how molecular genetics can inform evolutionary anthropology and give us insights into human origins. Can’t wait to hear him speak in person!

The Allen Brain Atlas is giving me so much right now.
Love it.
*pushes up glasses*

The Allen Brain Atlas is giving me so much right now.

Love it.

*pushes up glasses*

Eeesh, y’all!

A 45-minute lecture turned into 2.5 hours (through lunchtime) and I am STARVING!

It was good. But damn!

Excuse me while I run to the cafeteria so fast that I leave a cloud of dust in the shape of my body.

If ever you’ve wondered what I’ve been doing with my time at Rockefeller

The following is taken from the annual progress report I mentioned last week. Dr. Kreek is my PI (boss). I’ve wiki-linked some of the terms that might be unfamiliar. Also, it’s long and sciencey, so I’m giving you permission to skip the whole thing…or at least read the fifth and sixth paragraphs if you’re interested in how science can be used to confirm and reveal truths about the history of human populations. 

~

During my rotation in the Kreek lab, I focused on learning various genetic association and high-throughput genomic analysis tools and techniques. Specifically, my rotation project was to characterize a newly available cohort of human subjects from Grenada, who are currently participating in an addictive disease gene association study, with regard to genetic admixture and population structure/stratification (if any). Dr. Kreek and I decided that this project would be appropriate for me since it would give me the opportunity to make use of a number of genomic analysis tools and because it would dovetail nicely with my own personal interest in genetic ancestry research. Additionally, there are few studies of admixture in Caribbean populations outside of Puerto Rico, Jamaica, and the Dominican Republic; characterization of additional Caribbean populations could lend power to future association studies in admixed populations in the Americas.       

Since considerable admixture between European, African, and Native American populations has occurred in the Americas (particularly in the US and the Caribbean), and since the Grenadian population is largely of African with some European descent according to self-reports (similar to African Americans), I compared the Grenadian population to previously characterized African American cohorts from the New York and Las Vegas metro areas to highlight specific similarities and differences between the two as well as to determine whether the Grenadian sample would be most appropriately used when combined with the African American samples or as a separate group unto itself. To do this, I used a panel of Ancestry Informative Markers (AIMs) that are included as a part of an addiction gene SNP array that Kreek Lab uses for association studies. These AIMs consist of a set of unlinked SNPs that significantly and reliably in frequency between different putative ancestral populations. They are distributed across the genome such that a reasonable estimation of both group and individual ancestry proportions.

I isolated and prepared DNA from blood samples collected from study participants in Grenada and shipped to the Kreek Lab. After preparing the samples, I used the Illumina GoldenGate genotyping platform to determine SNP genotype for each of the samples. Once the samples were genotyped, I ensured the validity of the genotyping data by using Illumina’s GenomeStudio software to evaluate and edit SNP calls and clusters, removing unreliable or uninformative markers.

After validating the data, I calculated population and individual admixture proportions using the Structure software package, which uses a model-based (admixture versus no-admixture assumed) clustering method to estimate the number of subpopulations in a given sample and assign a probability of membership in each subpopulation for each subject. In my analysis, I assumed that each individual could be placed into subpopulations derived from genetic contributions from any of seven major ancestral populations: Native American, European, Middle Eastern, African, Central Asian, Far East Asian, and Oceanian. These populations are defined from SNP genotype data from the Human Genome Diversity Panel database, made available by The Foundation Jean Dausset-Centre d’Etude du Polymorphisme Humain (CEPH), from which SNP frequency data from 1050 individuals, representing 52 worldwide populations. These data form seven main SNP clusters that correspond to the seven assumed ancestral populations. By comparing the AIMs analyzed in my sample to the same set of markers in the CEPH dataset, I determined the percent contribution from each of the seven ancestral clusters for each of the individuals in the Grenadian cohort.

Overall, I found that our Grenadian cohort is 1) mostly African descended, with modest contributions from Europe, the Middle East, and Central Asia, and negligible contributions from East Asia, Oceania, and the Americas, 2) most of the non-African contribution is concentrated amongst a few individuals, and 3) its overall composition doesn’t significantly differ from our African American cohorts and so it can be combined with them to increase the total number of African admixed individuals in our association studies. Dr. Kreek and I are planning to write up a letter detailing my analysis for submission to an appropriate public health journal, most likely a PAHO publication like the Pan American Journal of Public Health.

In addition to learning genomic analysis tools, this project also allowed me to become better acquainted with using known anthropogeographic histories to identify populations that can potentially yield useful data and informative comparisons in genetic association studies as well as understand how to create relevant association paradigms. For example, admixture in our Grenadian cohort seems to reflect Grenada’s British/Spanish/French colonial legacy, a legacy that’s reasonably similar to that in the US, both having a past economy that was in many ways dependent upon slave—and later immigrant and indentured—labor. By taking these sorts of correlations between historical population dynamics and genetic admixture into account, I’ve learned how to avoid comparing closely similar groups in ways that are uninteresting. Taking this point further, I’ve also learned how to identify fine differences in similarly admixed populations that can be used to answer more specific or nuanced questions. A good example of this is my discovery that, while US and Grenadian African admixed populations are very similar in gross, Grenada differed slightly from the US in the specific amounts of Central and South Asian admixture proportions, reflecting an earlier abolition of slavery and a resultant more common use of indentured servitude—in this case involving laborers from East Indian and Turkic populations—in Grenada and other Caribbean islands. These differences, while not so important when comparing groups with regard to predominantly African versus predominantly non-African ancestry, could be potentially confounding or important in direct comparisons of African admixed populations.

I’m currently concentrating on three additional projects in the Kreek lab: 1) I’m characterizing another newly available admixed cohort from Sweden in the same way that I characterized the Grenadian cohort. This particular group is predominantly of mixed Swedish and Surinamese ancestry, so I’m expecting to find a more considerable contribution from Native American ancestral populations, less relative contribution from African groups, and a modest contribution from East Asian, Turkic and South Indian groups, reflecting population dynamics more particular to Central and South America compared to North America and the Caribbean, 2) others in the lab have found specific opioidergic gene promoter methylation patterns that seem to segregate along the lines of ethnicity combined with drug abuse versus non-abuse in our US cohorts. I plan to examine the Grenadian and Surinamese cohorts to see if I can find the same patterns in these populations, 3) for my thesis project, I’m planning on introducing a developmental/stem cell biology aspect to Dr. Kreek’s studies of the effects of acute versus chronic opiates on addiction behavior-mediating brain regions and the establishment of the opioid-dopaminergic axis. It’s known that chronic exposure to opiates can negatively affect both the developing brain as well as homeostatic and functional generation of new neurons and glia in adults, but the mechanisms by which this happens are largely unknown. At the moment, I’m planning to investigate opiates’ effects on neurogenic and gliogenic cell populations in various hippocampal and ventricular regions, most likely with a focus on either the transcriptional networks involved in proliferation, survival, and differentiation in those cells, or a focus on functional epigenetic changes brought about in relevant gene regions as a result of acute versus chronic opiate exposure.

Things I need to do within the next 36 hours: 
1) Write up my annual PhD candidate progress report.
2) Convince a leading opiate addiction expert that I can construct a tractable thesis project centered on the effects of chronic opiate exposure on the dentate gyrus of the hippocampus.
3) Convince a leading stem cell expert that I can construct a tractable thesis project centered on the effects of chronic opiate exposure on specific stem and progenitor cell compartments within the dentate gyrus of the hippocampus.
4) Convince a leading chromatin biology and epigenetics expert (and potential Nobel laureate) that I that I can construct a tractable thesis project centered on the effects of chronic opiate exposure—as mediated by alterations in chromatin structure and epigenetic machinery—on specific stem and progenitor cell compartments within the dentate gyrus of the hippocampus.
5) READ READ READ so that I can do 2, 3, and 4 without sounding like an idiot.
So I’m gonna be super responsible and have a Red Stripe at 2:40 in the morning. 

Things I need to do within the next 36 hours: 

1) Write up my annual PhD candidate progress report.

2) Convince a leading opiate addiction expert that I can construct a tractable thesis project centered on the effects of chronic opiate exposure on the dentate gyrus of the hippocampus.

3) Convince a leading stem cell expert that I can construct a tractable thesis project centered on the effects of chronic opiate exposure on specific stem and progenitor cell compartments within the dentate gyrus of the hippocampus.

4) Convince a leading chromatin biology and epigenetics expert (and potential Nobel laureate) that I that I can construct a tractable thesis project centered on the effects of chronic opiate exposure—as mediated by alterations in chromatin structure and epigenetic machinery—on specific stem and progenitor cell compartments within the dentate gyrus of the hippocampus.

5) READ READ READ so that I can do 2, 3, and 4 without sounding like an idiot.

So I’m gonna be super responsible and have a Red Stripe at 2:40 in the morning. 

This is me attempting to give a fuck about tubulin because I have to give a microtubule-themed presentation on Tuesday morning. I have something to talk about, but it’s not very exciting and oh my god I am so bored with this shit.
Also, I got new glasses this weekend. 

This is me attempting to give a fuck about tubulin because I have to give a microtubule-themed presentation on Tuesday morning. I have something to talk about, but it’s not very exciting and oh my god I am so bored with this shit.

Also, I got new glasses this weekend. 

I knew this day was coming. 
If I’m going to get into the nitty gritty of bioinformatics, I’m going to have to learn C++.

I knew this day was coming. 

If I’m going to get into the nitty gritty of bioinformatics, I’m going to have to learn C++.

I’ve been aligning sequence data all day, so in ten minutes, I’m going to go get drunk at RockU happy hour.*
*I would have gone anyway, but I like to justify my drinking. 

I’ve been aligning sequence data all day, so in ten minutes, I’m going to go get drunk at RockU happy hour.*

*I would have gone anyway, but I like to justify my drinking.