joshuamcginnis

My cofounder and I are working on a synthetic biology startup concept targeting rare diseases. We're both genetic and microbiology generalists with a desire to dedicate ourselves to improving the human condition.

I find it serendipitous that we just had a two hour call today discussing our desire to work on creating a treatment for one or more rare diseases.

The one area we lack expertise in is the regulatory and commercialization pipeline. If someone reads this and is interested in speaking with us about how we can work on this (or other) rare disease and could offer the mentorship we need to ensure our work can actually reach the hands that need it, please email me: josh@everymanbio.com

We'd consider a non-profit model if it makes sense.

Thanks man!

We used Guppy for basecalling, which is neural network based and used to turn raw signal data into the predicted bases. There're no guarantees of accuracy, only tools to determine and assess quality. One major way of assessing accuracy is to compare the subject genome with other similar reference genomes and denote the high-degree of homology in highly-conserved regions.

There are quality checks throughout the entire process, starting from the raw read quality scores returned directly from the sequencer all the way to fully assembled genome completeness. In our paper, one of the tools we used for this is called BUSCO[0] which scored our assembly at 97.9%, a relatively high score for de novo assemblies.

[0] https://pubmed.ncbi.nlm.nih.gov/31020564/

I did a HMW extraction kit on the DNA and used a gel to estimate the volume of HMW DNA. Yes, you need to be able to run a gel, but I'm not sure what the expectation is from folks; that you just place a random piece of non-sterile tissue on a chip and have it do the extraction, sequencing and assembly? That seems like an unrealistic expectation.

What do you mean by it's always a few years off? Nanopore will allow you to do high-quality genomic sequencing _now_, in a home lab if you wanted, for less than $3K. If you amortize the 3K by the number of genomes you can sequence on the same flow cell, the price per base or per genome falls precipitously, depending on the size of the genome of course.

That's not true. I just did a high-quality sequence and assembly of a new species of fungus from my home lab using nanopore. You can see all my code used for assembly and analysis that will be referenced in a paper I plan to publish in Jan here: https://github.com/EverymanBio/pestalotiopsis

A qubit or fluorometer isn't required. You can use a simple DNA ladder to measure the relative quantity and quality of DNA that's good enough for nanopore sequencing. I just did a full genome sequence of a novel fungus using this exact approach.

I'm doing a small enough volume that automation isn't quite needed yet. The process is basically creating a soil dilution, culturing some special media broth and then plating samples the next day. If this small experiment shows promise, there's talk of implementing something like Opentrons.

Glad to hear of your interest in bio! I haven't delve much into the business side, but that is something I'm planning to get into on my YouTube channel and Instagram (both are under EverymanBio).

I'm a SWE turned diy biologist and among the services I offer is bioprospecting for biotech startups. My most recent client hired me to gather soil samples from different biomes and running assays from my home lab to determine if there are any enzyme-producing organisms of interest.

How does one become a "skilled seed collector"? Are there jobs for them?

I've considered responding with a link to the "Criticism of Facebook"[1] wiki. Even if only half of it is true, it's still pretty horrendous.

https://en.wikipedia.org/wiki/Criticism_of_Facebook

I'm an indie researcher developing a diy-friendly approach to genetic engineering of mushrooms [1][2][3]. If anyone is interested, I'd be happy to provide a piece of the same slime mold species (Physarum polycephalum[4]) referenced in the article and used to study fungi memory and intelligence. It's pretty easy to grow and the only food it needs is oats.

The best way to send me your request is probably to send me a DM on Instagram or to email me (josh@everymanbio.com). Depending on how many requests there are, it may take me some time to get it to you - but I will.

A few $ donation for shipping would be helpful, but not required.

[1] http://everymanbio.com/

[2] https://www.instagram.com/everymanbio/

[3] https://youtube.com/everymanbio

[4] https://en.wikipedia.org/wiki/Physarum_polycephalum

Hi friends,

I'm Josh, the video creator and founder of EverymanBio. I created this video to show that it's possible to do real and meaningful genetic work in a less-than-ideal environment.

Although this video is focused on showing the process of "dna barcoding"[1] some wild fungi that I isolated from my local beach, it's the first of many that I'll be publishing to help folks get started with diy genetic engineering.

DNA barcoding provides a wealth of opportunity for gaining new skills and building out your lab. It's truly a great place to get your feet wet with learning cutting-edge biotech.

I hope you all find it helpful.

- Josh

[1] https://en.wikipedia.org/wiki/DNA_barcoding

I use two microbiology and mycology books I bought on OfferUp for $10, YouTube and papers. The vast amount of my learning comes from breaking larger technical goals into a series of smaller hands-on projects and then troubleshooting my way through. It's hard to give general advice on synbio since it's such a broad field and my journey principally involves a focus on fungi. In my case, I learned to grow all kinds of mushrooms and fungus at home. That lead me to learning DNA barcoding of fungi which has now lead me to DNA transformation of fungi. Feel free to send me more info about the direction you want to head in and I'd be happy to give you some feedback.

Absolutely. This is probably the best and only way to start.

My idea is to essentially be the glue and build the interface.

Agreed! And if it were complemented with added information about the organisms transcription machinery (promoters, terminators, etc), it could empower folks to generate DNA to test a new or modified metabolic pathway in a manner that's never been tried before.

The database would definitely need to define some boundaries and limitations, but I still think there is much opportunity in coalescing well-defined metabolic and genetic data and empowering folks to generate feasible genetic constructs.

> Have you tried applying your hobby towards reducing the cost of healthcare in America?

That isn't my stated goal, but I would imagine that sharing how to genetically engineer an incredibly powerful organism to express heterologous genes for less than $3000 in a kitchen lab could open up many possibilities!

> Could you diagnose what kind of flu virus you have?

Is it possible to extract DNA from a bodily fluid, perform PCR and read the sequence results to determine flu variant? I'd have to check on if there is a known DNA sequence that barcodes flu viral variants, but presuming there is, then yes - all of this is possible from a home lab currently.

That's a great list, but it's not just about annotated metabolic pathways; there also needs to be information about the gene(s) that have been characterized as being involved in those pathways, along with information about the source organisms and potential target organisms for production. Same with respect to substrates needed for intermediary pathways.

For the last year, I've been self-learning synthetic biology by working to become one of the few people to have ever genetically modified fungi in a diy lab environment[1][2][3]. It occurred to me that genetic engineering is largely a process of hacking biosynthetic pathways; that is, we take heterologous genes from organisms which have evolved novel biochemical pathways and we put them into other organisms that are really good at biosynthesizing those compounds at-scale (like Saccharomyces cerevisiae aka yeast).

One thing I've observed is there seems to be no universal well-annotated structured database for biosynthetic pathways. Updates and additions to known pathways are published unstructured in papers, often in graphical form, presenting even more challenging for structuring the data.

Were this to exist, it would be possible to build an app that let you easily design DNA plasmids for testing all kinds of incredible biosynthesis experiments. For instance, it would be able to select an organism [E. coli], enter your starting substrate [glucose], select a desired metabolite [psilocybin] and out would come a DNA sequence for a plasmid that contains are the necessary parts, promoters, genes and terminators for transforming E. coli to produce psilocybin.

In my opinion, such a tool could profoundly impact science, industry and human well-being.

[1] http://everymanbio.com/

[2] https://www.instagram.com/everymanbio/

[3] https://youtube.com/everymanbio

If my memory serves me correctly, I once a used a digital try-on app from an online glasses retailer and they had me hold a common item with a known width (something like a credit card or drivers license) in front of the cam within a bounding box. It could guess the location of my pupils but allowed me to drag the pupil location markers to the exact centers. Calculating pupillary distance was then just a matter of using the distance in pixels between the pupils and converting them to mm using the ratio of pixels to mm of the card in the previous photo.

Nice work! This is really cool. Does it have the ability to create job "profiles" so that you can create different sets of application data to use in different (but often related) jobs? I think that'd be a really cool feature, as well as auto-generating or suggesting content for job titles, description, etc.

I recall hearing about one contestants strategy for recalling the most digits of pi using this technique. He said he'd imagine a room with many objects in it. He'd assign 100 digits on the light switch, 100 digits on the top drawer, then the next drawer, and so on until reciting was just a matter of walking around the room in his mind and reading off the numbers from the objects in the correct order.

I wonder if the author has considered taking a crack at passage 4 of the Kryptos cipher.

https://en.wikipedia.org/wiki/Kryptos

Just picked up a Thinkpad P14s with the 4750u (8 core 16 threads) for about $600 using corporateperks.com discount. Spent another $250 for 1tb m.2 and 32gb ram upgrade. The value is tremendous.

One reason for this is that corn subsidies have created an excess supply of corn-based food derivatives (e.g. corn syrup) for years, driving down costs and creating an incentive to use cheap corn-based ingredients across the entire food supply.

I’ve been shocked by the old plastic slides at McDonalds so many times as a kid that I salivate whenever I hear the word.