Dear Shambolic Oligarchs: Here’s What I Did This Week

You wanted it, so here it is. Good and hard.

On Saturday night, I received an email from the anonymous pseudo-government entity known as HR, requesting a five item statement of work for the past week. Here, speaking in my voice as a private citizen of the Free State of Maryland, is my response.

1) I have a concept of a plan for bringing down the price of eggs. On Presidents Day, I worked from home to design a fusion of the receptor binding domain of influenza H5N1 genotype B3.13 hemagglutinin to a stabilized Helicobacter pylori ferritin scaffold¹. The sequence of the synthetic nanoparticle was subjected to extensive optimization for expression in yeast, so part of my week was spent refreshing my knowledge of yeast molecular biology literature. The synthetic ORF - with or without ER signal - will be moved into 2µ expression plasmids I developed encoding synthetic GAL10 or MAL32 promoters. Induced yeast will be fed to chickens, in hopes of rendering them immune to bird flu.

2) A recent paper from a group in China teaches that oral administration of yeast expressing surface-displayed bird flu antigens can protect chickens against a lethal challenge. In parallel to the ferritin constructs, I also spent time this week building on Lei and colleagues’ findings by designing a full H5 ectodomain appended with a glycosylphosphatidylinositol anchor. It seems conceivable that multifold cells in the chicken small intestine will be able to use sialylated glycans to tear away lipid-anchored HA trimers and transcytose the antigen for presentation on follicular dendritic cells in underlying lymphoid structures. This could be an improvement over the covalent Aga2p display used in Lei et al. I’m currently in the process of surveying the scientific literature to achieve a better understanding of other design parameters. For example, this past week I scheduled teleconferences and physical workplace discussions with colleagues who helped me brainstorm a concept of a plan in which the symmetry mismatch between hemagglutinin and neuraminidase could be used to zipper together a kinked 12 x 12 array using a scaffoldless Spytag approach. Another emerging idea we’re playing with is to use the hemagglutinin-neuraminidase tetramer of Newcastle disease virus (against which chickens are routinely vaccinated) as a symmetry-mismatched recall antigen that could help rapidly elicit de novo responses against HA trimers.

3) In a separate line of work this week, I’ve begun an effort to learn the complicated search syntax for Google BigQuery so I can extract metadata from NCBI SRA cloud records. This is the final step before uploading 20 TB of data representing 750,000 SRA records into a federal cloud repository. The upload will enable scientists around the world to quickly search for viral sequences in various datasets, including de-identified human cancer datasets. The exceptionally skilled bioinformatic scientist who had been spearheading the upload is unavailable because he’s embroiled in emergency damage control after losing a member of his small and highly interconnected team in the Valentine’s Day Massacre. I’m worried more staff members (such as myself) will be randomly fired and I won’t be able to complete the upload. It took several years and many millions of CPU hours to compress the library into a laptop-searchable form. This incompetent HR clown show you guys have been putting on is threatening to flush the whole thing down the toilet. This is not what efficiency looks like.

4) I enjoyed two workdays in which I distracted myself from the incompetent clown posse with the engrossing task of using HHpred and AlphaFold to deep-annotate Pox mesodorylaimus185453, the first known poxvirus of nematodes. The most interesting observation is a homolog for interleukin-6. This comparative virology discovery provides basic science information about the hidden mechanisms viruses have been using to manipulate immune responses for hundreds of millions of years. At a translational level, nematode poxviruses might one day be useful for treating parasitic worm infections.

5) A colleague down the hall pretty much singlehandedly developed a cure for a rare form of cancer called ocular melanoma. She’s among the strongest, most disciplined scientists I’ve ever worked with. My unbreakable colleague was fired in the Valentine’s Day Massacre. To reduce the mounting risk of experiencing workplace anger management issues, I used work hours to re-read MLK’s “Loving Your Enemies” sermon.

There’s another reason why you should love your enemies, and that is because hate distorts the personality of the hater. We usually think of what hate does for the individual hated or the individuals hated or the groups hated. But it is even more tragic, it is even more ruinous and injurious to the individual who hates. You just begin hating somebody, and you will begin to do irrational things. You can’t see straight when you hate. You can’t walk straight when you hate. You can’t stand upright. Your vision is distorted. There is nothing more tragic than to see an individual whose heart is filled with hate.

I also refreshed my memory of the complementary self-help advice in FDR’s 1936 Madison Square Garden speech.

We had to struggle with the old enemies of peace—business and financial monopoly, speculation, reckless banking, class antagonism, sectionalism, war profiteering. They had begun to consider the government of the United States as a mere appendage to their own affairs. We know now that government by organized money is just as dangerous as government by organized mob.

Never before in all our history have these forces been so united against one candidate as they stand today. They are unanimous in their hate for me—and I welcome their hatred.

I should like to have it said of my first Administration that in it the forces of selfishness and of lust for power met their match. I should like to have it said of my second Administration that in it these forces met their master.

Spending the workday writing this email helped me renew my long-term professional commitment to serving as a happy scientific warrior in the eternal struggle against organized money².

1. Anybody who can decode this intentionally abstruse jargon - and who has critiques or suggestions on chicken vaccine strategies - should please post comments! That’s kind of what this blog is really here for. You can also reach out to my easy-to-find work identity… assuming I don’t get randomly fired this week.

2. Song of the day: “Seven Devils” by Florence + the Machine