Postdoc, Boyden lab, MIT. Synthetic bio, weird microbes, physics. Engineering complex systems with evolution. High-dimensional optimization. Too verbose for twi
So so so so excited to share this!
This preprint summarizes my journey of trying to engineer the brain parasite Toxoplasma gondii to deliver therapeutic proteins into neurons, together with
@OdedRechavi
and
@SheinerLab
1/n
#bioRxiv
Excited to share that in June I will be moving to MIT to start my postdoc with
@eboyden3
! Looking forward to work towards turning some scientific dreams into reality.
Also - would be happy for any Boston recommendations!
MIT researchers have developed a computational technique that makes it easier to engineer useful proteins - including ones that could be used to measure electrical activity in the brain.
This project was a huge part of my life for the past 5 years, and it taught me a lot, about science, about myself, and about what excites me the most in science. Looking forward to hear your thoughts and comments! 14/n
Focusing on MeCP2, the protein missing in Rett syndrome, we show that our parasites can deliver MeCP2 to neurons, and we can even see it binding DNA in their nucleus the same way normal MeCP2 does! 10/n
Thanks to my mentors
@OdedRechavi
and
@SheinerLab
, everyone in both labs and especially Karoliina, our collaborator Stuart Cobb and everyone who helped along the way. Living between Tel Aviv and Glasgow wasn't easy, but being surrounded by friends made the whole difference
I think there is also an important lesson here on the vast untapped potential that lies in expanding synthetic biology beyond model organisms. Thank you
@datreeio
for emphasizing my musing about this in his piece
My primary thesis for bioengineering - yeah what you cannot create you cannot understand, but there is plenty that you can create without first understanding it
We noticed that these special skills of Toxoplasma answer the exact problems that hinder the delivery of macromolecules to the brain. We therefore wondered if these mechanisms can be harnessed for the delivery of therapeutic protein to the CNS. 7/n
We take an alternative approach to brain delivery - instead of engineering a synthetic solution from scratch, we figured out how to harness a parasite that naturally evolved to do exactly that
So we tested different secretion systems and different protein configurations until finally we found some that were secreted. Through these attempts, we also managed to show some cool things about the mechanism by which Toxoplasma secrets proteins to the host. 9/n
But we believe that by harnessing what was developed and perfected by this parasite for its own needs, we can provide a new method for delivery of therapeutics to the brain, which overcomes many of the hard challenges faced by current ‘man-made’ drug delivery systems. 13/n
Toxoplasmosis can be dangerous in people with weakened immune systems, but in most people infections are asymptomatic, and aren’t even noticed. In fact, it is estimated that a third of the human population are chronically infected with Toxoplasma. 3/n
Was surprised to discover I was selected as one of Israel's "100 most influential people"! Which lasted about 5 minutes before the post was corrected to tag the real Shahar Bracha that actually got the award
Using parasites makes a lot of sense- our bodies are complex, but parasites evolved through intensive natural selection to modify the human body in remarkably specific, robust, sophisticated ways. This is often the exact definition of what we try to do in medicine & biotechnology
This is important for showing that the protein Toxoplasma secrets is functional and could potentially replace the missing MeCP2 in Rett syndrome neurons. 11/n
This wasn’t a straightforward journey though, because Toxoplasma is quite a weird organism (an apicomplexan protist), and its not fully understood what makes some protein secreted and some not. 8/n
@datreeio
@eboyden3
It has been a long challenging journey, and seeing all this work come to fruition has been unimaginably satisfying. Grateful for all my amazing collaborators, and hoping that this is just the start!
A special thing about Toxoplasma is that when it infects humans, it knows how to migrate into our central nervous system, bypass the blood-brain-barrier and persist in the brain for a very long time. 4/n
As a newly minted 25-year-old, today I learned how to screen-print, listened to punk while working on my PhD paper, got silly slippers, celebrated with mexican food and got into a mini existential crisis after coincidentally finding a first ever tiny white hair. Tired but happy.
Some nice Scottish views on the way back from
#IDRIS2019
.
Was a great conference, and it's always fun to meet and discuss ideas with fellow parasitologists, the diversity and interdisciplinarity of the research within the field always amazes me!
Had an intense &amazing time at the Gordon Research Conference &Seminar on host-parasite interactions, survived my first ever conference talk, had great poster conversations and met many wonderful people. The parasitology community is incredible and I'm so happy to be part of it!
These important skills were developed as an adaptation to Toxoplasma’s niche as a chronic intracellular parasite, through the co-evolution of Toxoplasma and its hosts. 6/n
Carrying home the hard drive with my new data like a precious newborn back from the hospital, terrified and excited and knowing full well I'm not going to sleep tonight
@datreeio
This was one the most challenging parts of this project. Making the process of harnessing and engineering a wider diversity of organisms could be an extremely high leverage point for enabling faster discovery and development of new tools and technologies for biology
Just got my vaccine shot! Thanks to all the healthcare workers, scientists, essential workers, WFHers, maskers, home-stayers and science communicators who are making this happen.
Just realized that one of my worst pitfalls in writing, writing way too lengthily, is actually me trying to artificially increase the resolution of the language by using too many words and subconsciously expecting someone to run a smoothing function on my text while reading it.
Had an incredible night at the Wise observatory in Mitzpe Ramon. We brought a 8 inch telescope and got to see Jupiter with its four moons aligned, Saturn (and Titan?) which looked like a surreal distant emoji of itself, some of our moon, and take a cool picture with the milky way
New covid vaccination tents and festive lights in Rabin square, Tel Aviv center. Country probably reached almost 10% of the population vaccinated today
Is there anyone working on possible organism/cell-based COVID-19 diagnostics? What about engineered systems with reporter that could detect RNA sequence in solution via an RNAi response?
#synbio
@kindofgeometry
@itamar_lev
In our philosophy of frugal science, we are sharing today our latest tool from the lab: a 20-cent electroporator, which we call an ElectroPen. Almost a year ago, when I started my lab
@GeorgiaTech
, a team of high school students
@lamberths_iGEM
led by
@jastandeven
reached out...
#Worm21
Announcing the first ever Int'l Worm Meeting to be held in a non-US location.
June 19-23, 2021, Glasgow, Scotland - organized by Barbara Conradt and me. With the legendary
@wormraiser
as Keynote.
Check out awesome venue below and importantly, the great party site!
So cool - Sequencing and analyzing DNA from ancient scrolls (made of skin) to fit them together & gain insights on life and religion >2000 years ago.
Got to watch how this brilliant project unraveled by lots of hard work & ingenuity from the team
@NeuhofMoran
Sarit, Hila, Or
Here’s a wild story on how we tried to piece the Dead Sea Scrolls “puzzle” by sequencing ancient DNA extracted from the animal skins on which the scrolls were written. Please read the
@CellCellPress
paper, retweet and checkout my short thread👇
@michael_nielsen
I didn't test it on GPT4, but for GPT3 I found you can ask it for instructions on how to get from one place to another by walking, and it will give pretty good instructions (including both things like "turn from SmallStreet1 to SmallStreet2" and "head south toward MainStreet")
There's a Blackout but the Rechavi lab don't care:
🎼Sitting 'round crying over a broken heart.. .. Even if we're just cloning in the dark 🎼 - Deep sequencing using a flash light!
@shaharbrr
Thesis-writing advice: find a really good book to read. You'll just want to finish every writing session as fast as possible and get it over with so you can go back to your book.
#phdchat
@ilex_ulmus
One pro of coming from a culture that is obsessed with reproduction (Israel) is that egg freezing for all women over 30 is subsidized (~$2-3k), and can even be free if you or your partner have medical reasons. Planning to take advantage of this the minute I'm eligible.
Check out our newest work! perplexed by "Transgenerational Epigenetics Inheritance"?
1. You may think "it's easy to understand how traits are inherited in worms, since these are the simplest model animals for studying genetics" - Well, it gets complicated…
@michael_nielsen
What I found cool is that it seemed like when it was missing knowledge about an area of smaller streets, it knew how to replace it with a more general "go south toward Main Street". It made more mistakes the further and more obscure the streets were, but I wonder how GPT4 fares
Awesome work from
@AndrewEMaclean
@SheinerLab
and colleagues, on the divergent respiratory mitochondrial protein complexes of Toxoplasma, and also a great demonstration of the power of careful biochemical characterization to uncover mechanisms of parasite-specific drug targeting
@OdedRechavi
@eboyden3
Thank you! And thanks for helping me become the scientist I am today, couldn't have dreamt of a better mentor for this wild ride of a PhD :)
@michael_nielsen
I was asking about travel between two small streets around Somerville that are 10 street turns apart, so it's unlikely this exact trip could be quoted from somewhere online, but it probably tried to assemble it from parts that were
@GiliGreenbaum
A new interactive repository that will improve evaluation and dissemination of model results. Accepts models in multiple languages, but requires no programming knowledge to run/distribute model analyses. Want your models to be accessible?