Our first paper is out in
@CellCellPress
! Led by
@born2raisecell
, we present a programmable reaction-diffusion system that generates synthetic protein waves, oscillations, and patterns for spatiotemporal circuit design and FM data-encoding in human cells.
Our first preprint is out! Led by Rohith Rajasekaran (
@born2raisecell
): “A programmable reaction-diffusion system for spatiotemporal cell signaling circuit design”
A visually stunning toolkit to build cellular radios that probe or control cell biology.
Finally, plasmids for tinkering with this system will be on Addgene shortly. If you're excited about this technology or just enjoy psychedelia, grab these reagents and do a transfection--within 24 hours you'll be tripping. We're so excited to see where imagination will take you!
I’m excited to announce that I’ll be starting my own lab in the biochemistry department at the University of Wisconsin-Madison in the near future!
@UWBiochem
@UWMadison
Our mammalian cell programmable reaction-diffusion plasmid pack is now on Addgene--everything you need to get started making waves, analyzing images with DSP, and interfacing with cell biology! Have fun and reach out if you need help/have questions 😵💫
We provide a foundation for complex protein-based spatiotemporal circuit design in living cells and an experimental test-bed for leveraging synthetic biology to explore reaction diffusion systems.
This is only the start and we're eager to share our tools with the community!
Excited and grateful to have received an
@NIHDirector
's New Innovator Award from
@NIH_CommonFund
to pursue our work on cellular radio circuits! This wouldn't have been possible without the hard work from all my students and the supportive community at
@UWBiochem
@UWMadison
! 🦡
Early-stage investigators proposed innovative high-impact research ideas for the
@NIHDirector
’s New Innovator Award. See the projects the awardees will pursue:
#NIHHighRisk
Excited we made the cover of this
@CellCellPress
issue celebrating cell biology. Inspired by patterns our programmable reaction-diffusion platform creates (), we used a multi-scale RD-algorithm developed by
@jonathanmccabeX
to render this cell-like image.
For Cell’s 50th anniversary, the celebrations begin with a focus issue on cell biology!
In the new issue you can read not only a variety of front matter about the past, present, and future of cell biology, but also featured research articles on a genome-wide association
We are excited to announce the 2020
#PackardFellows
in Science and Engineering! Over the next 5 years, these 20
@PackardFdn
Fellows will engage in groundbreaking scientific research and reach new frontiers of discovery. Meet the Fellows: .
The print edition of our paper on Lacrymaria hunting dynamics appears this week in
@CurrentBiology
! Even more data and analysis of these amazing eukaryotic cells than our
@BioRrxiv
submission. Check out the video abstract narrated by
@NEWCUPID
!
My lab's favorite
@TeamFoldscope
sampling spots freeze in the winter.
@UWBiochem
legend Ivan Rayment helped my amazing
@UWMadison
grad students drill under the ice, get samples and see what our favorite
#protists
have been up to. We found wild Lacrys right beneath our feet🎶!
Across different cells, we observed MinDE could produce waves, spirals, and turbulent patterns with periods ranging from seconds to minutes; fast standing oscillations; and Turing-type “leopard print” patterns of regularly-spaced stationary protein domains.
And one last thank you to our reviewers for super helpful feedback & comments, our amazing editor, and the synthetic biology community which has been super supportive of this work over the last year. This is only the beginning of what we're up to in this space, so stay tuned!
This project was spearheaded by my brilliant graduate student Rohith Rajasekaran (
@born2raisecell
). My mind is blown by how much Rohith accomplished experimentally and computationally with this project! Truly a next-level thinker and scientist destined for great things.
A big Wisconsin welcome to our two new assistant professors — Scott Coyle (
@CellRaiser_
) and Amy Weeks (
@scientistamy
)! Read about their research in our profile:
MinDE circuits produce a unique signal that acts like a “cellular radio”, emitting frequency-barcoded data that can spectrally separate single cells or sub-cellular compartments using digital signal processing tools like FFTs, FIR filters, or wavelets with a single fluorophore.
Cell biology is animated by the organization of proteins in space and time, but we lack tools that can genetically encode synthetic protein dynamics.
We repurposed a bacterial reaction-diffusion circuit (MinDE) for spatiotemporal circuit design in mammalian cells.
In MinDE, ATP-dependent membrane association of the MinD ATPase is antagonized by its ATPase-activating protein MinE. Schwille and Mizuuchi labs have shown MinDE patterning on bilayers in vitro.
We found that MinDE circuits robustly drive protein patterning in mammalian cells.
And finally, thanks to the
@UWMadison
Biochemistry Department
@UWBiochem
and David and Lucille Packard Foundation
@PackardFdn
for believing in my lab and our science. A playlist of all the videos supporting this paper is available here:
Finally met
@BEuplotes
in person at
#ascb2022
and had a blast talking science, protists, computation! Creative thinker with interesting ideas about p much everything. Check out his talk (Symp 8), and if you're looking for a stimulating colleague he's on the job market right now
my labmate
@pranavvyas94
has accidentally been growing these tiny little colonial marine animals in his aquarium—tbh I think they are a lot cuter than the sea cucumbers he was growing before...
There's one week left to register for the 2022 Central US Synthetic Biology Workshop via ,
@WIDiscovery
@UWMadison
! Talks are trainee-focused and the meeting has almost no registration fee making it easy to bring your whole group!
By connecting MinDE to endogenous pathways, we built circuits that could read out, perturb, or control cell biology.
We demo MinDE cellular radio circuits that amplify and broadcast frequency-barcoded cell state activity dynamics, using Protein Kinase A signaling as an example.
Motivated by a lack of tools for organizing proteins in space and time, we repurposed a bacterial reaction-diffusion circuit (MinDE) for spatiotemporal circuit design. Last year we preprinted this work and shared a detailed thread (below) -- so what's new?
Our first preprint is out! Led by Rohith Rajasekaran (
@born2raisecell
): “A programmable reaction-diffusion system for spatiotemporal cell signaling circuit design”
A visually stunning toolkit to build cellular radios that probe or control cell biology.
We created a plug-and-play platform that dynamically connects MinDE to other components using the chemically inducible heterodimerizer FKBP/FRB.
Coupling MinDE to other proteins generated new composite signals and enabled real time AM/FM signal modulation with LLPS payloads.
We identified simple rules for programming the waveform (frequency and amplitude) of a MinDE circuit’s signal at a genetic level by controlling the relative and absolute expression of the components. Behaviors could be further modified by targeted mutation to MinDE components.
@UWMadBiophysics
rockstar Chih-Chia (Eden) Chang (
@Eden81513688
) dreamed up so many creative ways to connect MinDE to other interesting components of the cell, including protein condensates and the microtubule cytoskeleton. Stay tuned for a very exciting story from him on this!
Headed back to
#cellbio2022
with lab members
@born2raisecell
(B605),
@MaggieXzj
(B693) and
@EdenChang_
(B115, MT structures mini-symposium talk) who will be presenting awesome work! I'll also be talking about our latest at the "Biological Time Control" subgroup. See yall there!
Congratulations to 2022 Glenn Foundation for Medical Research and AFAR Grants for Junior Faculty recipient
@JudithSimcox
, who will investigate the discovery of ceramide signaling as a regulator of
#energy
expenditure with
#aging
. Learn more:
@UWMSTP
MinDE can also act as a control-signal to synthetically reorganize native signaling.
Using the Listeria effector ActA as a payload, we built MinDE circuits that synthetically pattern the actin cytoskeleton in new structures and probe temporal constraints with dynamic signals.
Third: we've included a detailed "design manual" to help new users become familiar with reaction-diffusion systems, the MinDE components, and how they can be used to build and model more complex synthetic circuits. Length and timescales are super important to consider here!
One of the great things about University of Wisconsin-Madison is getting talented undergraduates or even high-schoolers in the mix. So proud of
@UWBiochem
undergraduate Tommy Gallateo and
@VelPhillipsHS
student Elliott Weix for their big contributions to this work!
Ingenious work led by my colleague
@deepak_me90
in the
@PrakashLab
to build a whole new type of vertical tracking microscope... Literally everything you put it in, from grains of sugar to single celled plankton, yields a new surprise.
First: this paper is bursting with new concepts and our amazing editor gave us the space and support to unpack and discuss these ideas fully. In particular, we've clarified the powerful frequency domain and time-frequency analysis image analysis tools, which really shine now!
Super excited to be part of the “Mechanics of Large Cellular Machines” subgroup at
#ASCBEMBO19
this year (Saturday, Room 151A, 1230-330). Come see fantastic talks on a range of exciting cellular systems that challenge us to bridge length and and time scales.
Loving that
@ChemRxiv
is tweeting out graphical abstracts for it's preprints-- would be awesome if this could be something we could start for
@biorxivpreprint
as well
Fantastic work from
@guille_rochelle
that blends physics, cell biology, and stunning microscopy to chart how ciliary organization at every scale helps keep our airways clear!
#mucus
Great thread highlighting some really nice natural and engineered examples of cooperativity (one of life's secret sauces) in TFs. Should do one for signaling scaffolds too...
1/n There have been an EXCITING recent papers highlighting the importance of LOW-AFFINITY binding and COOPERATIVITY among TFs. Let me highlight a few – come take a quick ride!
Congrats
@Eliott_Flaum
- 2nd year biophysics grad student in lab on passing her quals exam in flying colors. I am thrilled to have you in the lab! For celebrations, lab folks tried to rent a dog (Ellie loves dogs); apparently not possible. But on twitter, I found a cute dog.
Second: we added a new stability analysis to show that the frequency of an oscillation is quite consistent over the lifetime of a cell, even as it crawls around, changes shape or divides. We suspect drift in a cell's frequency may reflect underlying changes in its physiology...
Happy to share this perspective piece on what ciliates might teach us about building dynamic autonomous systems at the microscale:
And I had a blast sampling the lakes here in Wisconsin to find inspiration!
I am recruiting PhD students to join my lab
@univmiami
in fall 2021! If you are interested in working on biophysics projects in fascinating and enigmatic marine invertebrates, please email me. Please RT and spread the word!
#PhDposition
#biophysics
#biomechanics
Exceptional work that expands the scope of applications that synthetic notch receptors can be used for. The precision and tunability of the force-gating here is spectacular, and I suspect we are going to learn a ton about mechanobiology from these tools! Congrats to the authors!
@PrakashLab
Getting to work in the
@PrakashLab
was one of the most exciting and stimulating experiences I've ever had. I learned so much from so many incredible people. I couldn't have asked for a better post-doc than to be in this special place.
Super impressive work from
@BashorLab
@XiaoyuYang6
et al, providing a much-needed module and framework for engineering synthetic phosphorylation circuits in human cells--this is where the rubber meets the road for controlling interesting dynamic cell behavior. Great stuff!
My group will be exploring how molecules specify the systems biology of emergent behaviors in banal (i.e. human) and super exotic (i.e. protozoan) cells; and how we can exploit that understanding to build new types of biochemical machines and engineered cells.
@BEuplotes
an absolute classic... One of my favorite ways to chill out is to run flowtrace (
@wgilpin0
and
@Viveknprakash
) on a pond water sample to watch cells live out there lives as those trajectories
Congratulations to Judith Simcox on being named a a Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Scholar! Simcox is an assistant professor in
@UWBiochem
.
Read more:
Most of all, I’m super excited about my new colleagues (esp.
@scientistamy
) and all the scientific adventures I’m going to have. If I play my cards right they might even let me put a microscope inside a cow… 🔬🐄
Thank you to the incredibly thoughtful
@united
cleaning crew who found and rescued my laptop I accidentally left in the seat back pocket-- you made it so easy for me to get it back today and saved me from a whirlwind of anxiety; thank you!!! 🙏🙏🙏
beautiful work from
@MullinsLab
— great framework for thinking about how loading and unloading of components at the membrane yields differences from assembly in solution
Just posted a preprint of a review article that aims to paint a coherent picture of how branched actin networks self-assemble: "From solution to surface to filament: actin flux into branched networks"
#Biochemistry
#Biophysics
#CellBiology
#Cytoskeleton
For more insights on the paper, check out this fantastic dispatch written by cilia wizard Kirsty Wan (
@micromotility
) that provides great perspective and sets the stage for future work on extraordinary single-celled eukaryotic organisms.
I’m grateful for all the support and mentorship I’ve had from
@PrakashLab
, Lim Lab, and Doudna Lab, as well as my colleagues from CellDesignLabs to get to this point.
In a similar, anecdotal observation, lacrys strike each other all the time but never eat one another. However, in a mixed population in which some cells begin to die of starvation, dying lacrys will become consumed by their kin (see grisly vid). Some change is detected but what?
@mmslabodnick
@Eliott_Flaum
and I reproduced a very old result from an EM paper in her rotation that intact stentor is not recognized as food (they hit it but don't try to eat) but if you stab a stentor with a needle they will voraciously devour the chunks that get ripped off. unclear why?
I'm excited to share a good news in this otherwise trying time. The final version of our work single molecule microscopy of microtubule nucleation by γ-tubulin ring complex is up!
[1/n]
Awesome preprint by Tyler Ross from Matt Thomson's lab at Caltech: using an optically controllable in vitro aster system they are able to control force generating structures and program flows in the environment using patterns of light.
@BEuplotes
Its neat how they just twist off from one another, one getting the neck and the other getting the tail -- keep watching and you might see them conjugate, which is even more wild to see (two lacrys / one neck) and also involves twisting off, just at a different place.... 👀
Late to the party on repping this tweet but I can say from my own experience working with Aaron
@warpcorebreach
that this is guaranteed to be an exciting opportunity for anyone interested in the intersection of synbio and immuno. Big brain cool and important science for sure.
if you love gene editing and despise cancer, come join the team
@ArsenalBio
to lead research efforts to improve how we discover and manufacture our cell therapies for solid tumors!
(1/n) Latest pre-print from lab! Octopi; open configurable high-throughput imaging platform. Led by an incredible graduate student
@hongquan_li
- we crack puzzle of automated low-cost malaria diagnosis. Remember, malaria still kills ~1/2million people/year
@CellfOrganized
@biorxivpreprint
We were honestly shocked how many things you folks saw in vitro could happen in these cells. Rohith and I must have read your in vitro papers 1000 times over...
Super insightful framework stemming from 'cellular discretization' -- excited to see this deployed experimentally and perhaps some elements of this can also be extended to other reaction-diffusion settings!
In his 1952 classic, Turing showed that ≥2 interacting, continuously diffusing morphogens can spontaneously generate beautiful biological patterns. On a discrete cell lattice, we find that 1 morphogen is enough for stable spatially periodic patterns
@BEuplotes
Looks very trackable to me! For darkfield videos like this I find that a quick FlowTrace by
@wgilpin0
and
@Viveknprakash
from
@PrakashLab
makes the tracks super easy to see and is a great starting point for quickly getting intuition for the cell trajectories. Frantic indeed!
Great genomics story from
@UWiBio
arachnid wizards in Prashant Sharma's lab on why daddy long legs have such long legs. Research like this is one of many reasons why I love being part of a place like
@UWMadison
!
New (and first!) review from our lab:
@uwmadisonipib
@UWBiochem
grad student Clara Frazier and I wrote about recent developments in engineered peptide ligases for cell signaling and bioconjugation in
@BiochemSoc
Transactions:
Among the many things I learned an important one was that I should always have fluorescent beads in my handbag because you never know what interesting flows you can encounter:
thrilled to announce
@BEuplotes
paper showing that a single cell, Euplotes, coordinates its walking with a computational process implemented using microtubules. We like to think about cells as computers or robots, and this work shows they really are!
excellent review discussing how sequence diversity in signaling proteins — whether natural or human generated — can provide a wealth of information about how they function to connect inputs to outputs.
Remarkable results about mode of action / selectivity by CDK inhibitors that could not have been revealed without the innovative approach of measuring CDK complex stability ~inside~ living cells. Outstanding work pioneered by
@DrLPacka
and the Meyer lab!
#ThrowbackThursday
: MCB Professor Jeremy Thorner at the end of his Ph.D. studies in 1972, shortly before arriving as a faculty member here at Berkeley.
Submit your
#mcbTBT
photos here:
Simply outstanding work here; and a really creative application of optogenetic-based signaling controllers to study a higher-order emergent process like development
Our paper "Signaling dynamics control cell fate in the early Drosophila embryo" is out today
@Dev_Cell
! I'm *really* proud of the work & Heath Johnson, the postdoc who led the project. Read the published paper here (free access for the next 50 days):
@foodskop
@NeedhiBhalla
@born2raisecell
@BementLab
ohhhhh yes we've definitely chatted about this stuff : ) the parallels how the wave generators for native cortical actin dynamics his group sees are controlled and this system point to some universal themes for patterning
🔥New preprint! We hijacked secretion systems of brain-infiltrating parasites so they secrete therapeutic proteins inside neurons. We propose this could be used in the future to deliver drugs through the BBB as the parasite is mostly asymptomatic in immunocompetent individuals
@PrakashLab
I smile every time I see them in the wild -- it always makes me nostalgic for the first Foldscope outing you took me on that helped me remember why I loved science so much in the first place🥲 as well as how much scientific mystery there is in every drop of nasty water...
@dudin_o
@Eliott_Flaum
Never saw motility phenotype with any actin inhibitors- and we threw the book at 'em (
@guille_rochelle
had me try everything but maybe not working?). Dynamics appear driven by ciliary activity + anchoring. Nice review on peculiarities of actin in ciliates:
@dudin_o
Actin in ciliates isn't usually exciting (a downer for Team Actin at meetings) -- but helical microtubule cytoskeleton and contractile filaments (centrin) ass. with cell/neck morphology rearrangements during capture/engulfment are imo stunning!
@Eliott_Flaum
has taken great imgs:
@DumontLab
This is awesome Sophie!! Been excited to see the finished product ever since I saw
@lilanearhing
's poster on this at the GRC a few years back -- the parallels in this to how antagonism modulates signaling behaviors is uncanny (to me anyways haha). Gz!