Mitchell Lab
@mitchell_sysbio
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Systems Biologist trying to untangle Host-Drug-Microbiome interactions | PI at @UMassMed School | Trying to keep the BS to a minimum (not always succeeding)
Massachusetts, USA
Joined July 2016
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Pinned Tweet
Why are some non-antibiotic drugs toxic to bacteria 💊☠️🦠? Do they work like standard
#antibiotics
(ABX)? Our latest work by
@MarianaNoto
published
@ScienceMagazine
addresses this fundamental question (1/n)
15
116
355
I keep on preaching to my lab about the usefulness
@ChatGPTapp
for coding, but real-life demos might be more effective. A thread on a neural network we quickly developed to classify antibiotics sensitivity 🧵 (1/10)
10
102
565
So you (still) consider yourself a (micro)biologist. Another
#FridayLabChallenge
In 10sec, eyeball the colony number 🧵
320
32
343
Useful data for those working with the confetti strains that
@ATinyGreenCell
cloned and shared with us and many other (collected by
@MarianaNoto
) 🧵.
6
33
325
So you call yourself a microbiologist … quick Friday challenge (with surprising results). In 10sec, eyeball the colony number 🧵🧵🧵
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317
Hard to admit, but being a PI is not everything I hoped it would be … I’m sure this might resonate with other PIs out there
9
15
182
That was a tough one. There were ~2,500 colonies, most humans and machines considerably underestimated. Follow the thread for details and anecdotes ... 🧵
So you (still) consider yourself a (micro)biologist. Another
#FridayLabChallenge
In 10sec, eyeball the colony number 🧵
320
32
343
13
7
123
Finally out on
@eLife
! We show that bacterial evolved resistance against chemotherapy can reduce its efficacy in a treated host. Potential important implications for the
#Cancer
-
#Microbiome
field. By
@BrittanyRosener
and
@serkansayin_
& the Walhout lab
9
25
108
Our paper on syntrophic microbial communities is out on
@CellSystemsCP
. Congrats to
@MarianaNoto
@BrittanyRosener
and
@serkansayin_
. A quick recap of our findings on this🧵
8
34
89
Our paper on cell-cell variation in drug resistance in isogenic melanoma cells is out. Congrats to
@PayamKhoshkenar
and
@emily_lowry23
. A quick recap of our findings 🧵🧵🧵
4
19
86
With all the hype around single-cell/molecule/whatever methods, I’m still in awe by the simplicity and brilliance of
#OldSchool
assays like x-gal plates (though this specific one might be extremely important so I’m biased)
2
2
65
Final thoughts: 🤯 Great experience, blow my mind, ⏱️ saved us tons of time (took ~3hr), 👨💻 Will gladly share code/images if useful, 🔵 I started on the Blue place too, follow me there (10/10)
5
0
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our
@PLOSBiology
paper is out, we show how a
#Robot
,
@YouTube
and
@Twitter
can transform
#STEM
education and bridge geographical distances.
0
30
57
Most of us underestimated, none really overestimated (colony number was 118).
9
2
45
First publication of work done in our lab (
#microscopy
and auto. image analysis by
@PayamKhoshkenar
). Research was lead by the
@london_lab
.
Covalent Docking Identifies a Potent and Selective MKK7 Inhibitor.
3
8
45
Wow, beautiful work by Martin Ackermann’s lab on variation in gene expression in bacteria
@CellSystemsCP
:
1
19
41
@AnnaTesten
Why not sequence (WGS is 80$ with
@MiGScenter
)? I still have to pinch myself every time I realize that you can sequence 5 bacterial genomes for the price of a single antibody
4
1
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@AMartinezArias
I rarely get mixed in these (don’t know any of you), but setting the science aside, I think your writing was overly aggressive (and continues to be so in your reply). This reflects a toxic vide many ppl dislike and it does a bad service to the wider scientific community.
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@Ejike2
@ATinyGreenCell
@MarianaNoto
Absolutely! Although their striking colors make them ideal for
#STEM
education and less for research. Btw, we’re developing a
#ScienceOutreach
project now and we’ll share the curriculum as
#OpenSource
once the program is running.
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2
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machine (matlab code) got it almost right (undercounted by 2). Closest humans were equally close (overestimated by 2).
3
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Next time, eyeball the optical density of the bacterial culture (mid-log). Will be glad to hear of more ideas …
9
0
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We think confetti strains are a unique tools for educators and we actually planning a new
#STEM
#ScienceOutreach
program to follow our previous “Emergence of a superbug” project.
1
3
33
Proud of
@BrittanyRosener
from my lab for winning a poster award at the
@UMassMedical
/
@GSBS_UMassMed
retreat on her work on
#cancer
-
#microbiome
-
#drug
interactions. …and also for finally joining
@Twitter
0
2
32
Necessity is the mother of
#creativity
. My student Alex taped a magnifying glass to our tissue hood screen to see the
#cancer
spheroids he’s working on. Works great!
3
3
31
Together with more than 150 peers, I just (zoom) attended one of the *best* PhD defences I ever saw. Remarkable delivery under extrodinary circumstances by
@CruzgordilloP
from the
@TheLeeLab
.
0
3
28
Officially welcoming a new member to our lab, Alex Park is using
#MachineLearning
and
#NeuralNetworks
to develop a novel microscopy-based platfrom for pooled
#CRISPR
screens.
2
2
29
Honored to be receiving, with my PSB peers, the education recognition award for our Systems Biology course (Walhout,
@job_dekker
,
@TheLeeLab
,
@BrewsterLab
and Yilmaz). Teaching over a half of
@GSBS_UMassMed
PhDs on Quantitative Bio. and
@MATLAB
coding.
2
6
29
I love these small (and potentially) historic moments. Mariana (our new rotation student) is setting up a very unique bacterial
#GeneticScreen
0
3
27
A
@UMassMedical
Now piece on our
#STEM
outreach program with 250 high-school students. Our online
#robotic
platform allows remote students across 7,500 miles to evolve bacteria in our lab and identify mutations driving
#antibiotics
resistance.
0
10
26
Our joint opinion piece in
@trendscancer
following a fantastic
@NCIsysbio
and Xavier’s lab (
@sloan_kettering
) organized meeting. Cancer-Microbiome interactions are a new frontier for Systems Biology.
0
13
24
Glad to share our latest work on
#cancer
-
#bacteria
-
#drug
interactions just published on
@eLife
. Read the 🧵 written by
@serkansayin_
(first author!) to learn more:
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6
25
Using this
#WorkFromHomeChallenge
to train 40
@UMassMedical
staff and students on
#DataScience
. With generous free access from
@DataCamp
and
@athmapai
’s help we will cover skills from
#R
to
#RNASeq
analysis. Hoping this culminates in an online
@zoom_us
conference.
1
2
24
Very impressive study monitoring a defined
#microbione
in mice over 6-years!! Reveals adapation mechanisms and strain co-existance (sort of a
@RELenski
type
#LTEE
with a 12-species community and in-vivo).
0
13
23
Our lab, joining all labs in my department
@UMassMedical
, has contributed all of our
#PPE
(personal protection equitment) to
@umassmemorial
. Glad we can help. Thanks to "our boots on the ground” still on campus
@serkansayin_
, Cedric Diot, Nicki Fox and
@YuLiu_Sunny
3
3
23
30 year after
@RELenski
. Our
#scienceoutreach
on bacterial
#evolution
begins in 24h. Media and antibiotics are ready
0
7
21
All lab members collaborating on a
#pixelart
project (after bribing them with beer and pizza). Better photos tomorrow
0
2
20
Fantastic talk by
@arjunrajlab
from UPenn at our systems biology seminar. Justified the totally packed room.
1
0
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Congrats
@asanchez_lab
for really elegant work! Assembling *all* possible permutations of N microbes (with a multi-pipette) and evaluate their performance (they explore N=8, P. aeruginosa).
1
3
19
That’s it! We have a working NN classifier!! Next, we wrote a wrapper script that takes in new plate images and uses the trained neural network for classification of each well. It worked great!!! (9/10)
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@BladerLab
As Dylan said, The Times They Are a-Changin'. Just embrace the change. With beads you can “multiplex” (shaking 5 plates with each hand).
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@Prokaryota
I often tell my students that debugging failed PCRs is one of the best wax-on/wax-off exercises for biologists. Unfortunately, this reference typically fails to cross the
#GenerationGap
(as most of my other pop-culture refs)
0
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@serkansayin_
and
@MarianaNoto
are reopening the Mitchell lab. Extremely proud of them and of
@UMassMedical
for dealing with the crisis so carefully and responsibly
0
2
19
Brittany (
#NotOnTwitterYet
) and
@serkansayin_
from my lab are about to sequence genomes of evolved bacteria with
#MiniSeq
(thanks to
@athmapai
). This is our equivalent to "boldly go where no one has gone before”. Unbelievable that we’ll get to explore these tomorrow!!!
0
2
17
We are opening our
#DataScience
training to
@GSBS_UMassMed
students. We use a combo of
@DataCamp
and
@SlackHQ
to train (from R programing to RNAseq analysis). No prior programing knowledge needed. Student and fellow PIs
#RetweeetPlease
. Register here:
0
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Lastly, this paper is also the outcome of a very professional editorial process that truly added value to the process, pushed against unreasonable requests of the “reviewer
#2
” and helped us focus. Past tweets by others tell me many share this experience at
@CellSystemsCP
1
3
17
Sad to see Esther Rodman, our wonderful summer intern, leave. Thanks for launching our collaboration with
@ophirshalem
’s lab. You did great!
1
6
16
We designed a 10$ DIY OD reader (
#arduino
) and mailed these to 8 high-school classes for our online evo experiment:
1
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Many people are behind this success, but this is primarily the triumph 🏆 of
@MarianaNoto
who confronted a challenge that seemed truly intractable (study the MOA of almost 200 drugs) (18/19)
1
0
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Just found out that
@Addgene
has its own youtube channel. Its a fantastic resource (protocols, careers, faq, etc)!
1
6
16
We used a microplate reader to grow and measure absorbance over 16hr. Strains were diluted 1:200 from OD 1 into LB (rich media) or M9 (synthetic media) supplemented with kanamycin.
1
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15
Super exciting,
@serkansayin_
, my first student, passed his qualifying exam. Congrats Serkan!
0
1
15
Its official, the fantastic
@youklab
is joining our department at
@UMassMedical
, couldn’t be happier!
In Jan 2021, I'll be moving to
@Umassmed
to join the Program in Systems Biology (PSB) as associate prof. Superb place w/ great labs incl
@job_dekker
@mitchell_sysbio
@TheLeeLab
Walhout, Brewster, Shank +more. I thank PSB for the opportunity & my students for making this possible.
21
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100
1
0
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A very thoughtful perspective on Feedback in biological systems from
@HanaScientist
on
@CellSystemsCP
. Begins with what we know, continues with key unanswered questions and has a beautiful poetic ending!
1
2
14
The Golub lab (
@broadinstitute
) stares the elephant in the room straight in the eyes: Inescapable rapid evolution of cancer cell-lines across labs leads to diverse phenotypes and drug sensitivities.
0
7
14
Can't deny the aesthetics of auto liquid handling. One (small) step forward with our
@OpenTrons_
platform
0
6
14
We first made a simple plastic adapter that allowed us to quickly image microdilution plates with a standard document scanner (keeping plates in the same position) (4/10)
1
1
11
We manually divided the single-well images into subfolders by their phenotypes. Nothing fancy, drag and drop according to a decision of a human classifier (6/10)
1
0
13
@bykriscampbell
The Harvard Chan Microbiome in Public Health is having a one day online symposium soon (May 17).
1
2
13
This is what genetic testing w/o *any* regulation looks like. Great piece on genetic testing in pets by
@eenork
, Lisa Moses and Steve Niemi.
1
9
13
Brittany,
@serkansayin_
and our
@SingerInst
robot rocking a genetic screen after a long time. Always exciting to see high-throughput biology being made in a push of a button.
0
3
13
@blekhman
I see it as a kind of a “statement", like hipsters using a flip phones to show they aren’t swayed by technology or using a Mac to signal you’re an individual thinker
0
0
13
We wrote a
@matlab
script to segment plate photos, crop them, and save images of individual wells (by position). Scanning 40 plates generated a our training set (~4000 images) (5/10)
1
0
13
Better view of what we did while running a very slow gel
0
3
13
Wrapping up a day hosting Joao Xavier from
@sloan_kettering
. Heard about his fantastic
#microbiome
research while he drew analogies to soccer.
#YouHadToBeThere
1
0
12
Just finished a 1h online Q&A session with 75 high-school students on our
#evolution
experiment. Totally blown away by their insights.
1
4
12
Most labs score growth by eye, but that seems overly *tedious*. Since we have hundreds of plates to test, and a crave for tech, we decided to try out an
#AI
solution (3/10)
1
0
12
Take home message - if you see a dense plate, you’re probably underestimating the colony number 🧐🧐🧐
2
0
11
Just covered this paper in our journal club. Beautiful work by Erdal Topeka’s lab (
@UTSWNews
) on bacterial adaptation to antibiotics in mice GI tract (without evolving resistance)
0
3
8
Our
#STEM
project ends with a bang. Whole-Genome-Sequencing (
#WGS
) of an evolved bacterial strain homes resistance to an inactivating mutation in ompR. Special thanks to the 200 world-wide
#human
participants (and one
@Eppendorf_USA
#robot
)!
0
4
12
Late night pixel art at the lab (after a couple of beers)
0
4
12
We then used
@MATLAB
to fit a growth curve function and extract key parameters: doubling time, lag period, and yield (3 biological replicates per strain/condition)
1
0
12
Drug microdilution panels are a common method for testing bacterial
#antibiotic
sensitivity. Basically, you aliquot bacteria into multi-well plates with a different drugs and monitor growth after a day (2/10)
1
0
12
Welcoming Peter for a rotation in our lab (Brittany
#NotOnTwitterYet
is showing him around). He’ll be developing a method for bacterial genetic screens using
@illumina
#NGS
0
2
12
When added results from screen of non-ABX to the mix ▲◼️, almost all of them turned out to be disconnected from the ABX hubs. This was a key observation 🔑: non-ABX likely kill bacteria differently from standard ABX (10/19)
1
2
12
Our lab is celebrating. Esther joining a summer project, Brittany joining the lab, myself for grant submission,
@serkansayin_
for his qualifying exam and
@PayamKhoshkenar
for his contribution to a manuscript with collaborators.
0
0
12
If you’re interested in drug resistance (across fields), consider attending the Gordon conference
@kaushans
and I are chairing this June (we have spots for contributed talks)
2
1
12
Over-estimation of stress-induced mutagenesis puts evolvability in question (in bacteria). Great insights *simple* and beautiful experiments. Way to go
@PLOSBiology
. CNS needs to publish more of these!
2
6
10
Data points for yield should be taken with a grain of salt since the colors of the chromoproteins might impact absorbance (especially at high confluence).
1
0
10
#Evolution
stops for no one.
@serkansayin_
on his way to dilute our drug resistant bacteria for another day of adaptation.
1
3
11
Just added another
@ProgMolMed
from
@UMassMedical
to our
@DataCamp
training on
#DataScience
. Almost 80 trainees, and some of them are racing forward. I strongly recommend Bio departments world-wide to consider this for remote training for wet and dry bio students.
1
3
11
Asked 23 people (kids, phd students, techs, PIs, and postdocs) to try it independently. Closest estimate won a bag of chips. 🏆
2
0
10
Next, we prompted chatGPT to generate
@MATLAB
script for a neural-network that classifies hand-written digits (an input format is very similar to our single-well photos) (7/10)
2
0
10
Tour-de-force detective work on cellular memory in yeasts by
@KevinVerstrepen
and
@swainqbiolab
. *Beautifully* written and leaving room for a sequel work. Glad to see that
@eLife
gets that not *every* paper in cell bio. needs to end with a mechanism.
0
4
11
We modified the code slightly (e.g., we have only 8 alternative classes while digits have 10) and trained the neural network on our training set (8/10)
1
0
10
How symbolic, 75 years after Luria and Delbruck
@serkansayin_
and Qi Yang in my lab are using
@Eppendorf_USA
#robots
to do the same (just way more throughput).
0
1
9
@serkansayin_
just gave a killer talk (and great q&a) at the
@UMassMedical
retreat. You made the lab proud!
0
2
10
Finally the S. cerevisiae strikes back. Still a few K generations behind
@RELenski
's LTEE but “a journey of a thousand miles begins with a single step"
The longest evolution experiment in yeast is still going strong! It confirms findings from the famous long-term evolution experiment in E. coli and identifies interesting differences. Retweet if your network should learn about this window into evolution
0
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0
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9
3 years ago my lab had its first taste of
#NGS
. Since then our hunger for sequencing doubled every 6 months. As a postdoc I swore by quantitative microscopy … as a PI I feel that my journey towards the dark side is now complete ⚫️
0
0
10
Our brief
@RELenski
#outreach
#evolution
project ended. Results from 96 adapted strains (evolved by 150 high-schoolers across the Atlantic accessing our online robotic platform).
(resistance inferred from fifty plates like this one)
1
3
10
@DrHazmatic
🚶Walking station desk, sounds absurd, but gets you moving daily and 🖍 Crayons, they work on white boards and are erased w/o a mark with a wet cloth (even after 1yr)
1
0
10
Exciting! First time a student shows original work from our lab.
@serkansayin_
just gave a fantstic talk on
#ScienceOnTap
(room was packed).
0
2
10
The program in systems biology finally has its own
@EpilogLaser
cutter. Looking forward to hack biology hardware
0
3
9
I have a new fetish, shadowing
@MATLAB
intro lessons and realizing that even a decade-old user like me, can still learn new things on its basic functionality. Great lesson by
@BrewsterLab
on the math behind
#ImageAnalysis
(as part of our
@GSBS_UMassMed
course on
#SystemsBiology
)
0
0
9