Itai Yanai
@ItaiYanai
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Professor at the NYU School of Medicine. Co-host of the 'Night Science Podcast' @nightsciencepod
NYU, School of Medicine
Joined January 2015
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Published today! We found that cancer cells adapting to drug treatments don't simply switch from a sensitive to resistant state; instead there's a ‘resistance continuum’ of resistant phenotypes with epigenetically reprogrammed states. 🧵⬇️
@Gustavo_SFranca
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New Nature paper provides evidence that science has become less innovative since the 1950s. The authors suggest reversing the trend by:
1. reading widely,
2. focusing less on quantity of papers, & more on research quality,
3. taking year-long sabbaticals.
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I must admit that this annotated Nature abstract remains a useful recipe for constructing a summary paragraph. I show it to my students every time we get started.
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I met a scientist who was just trying to do good science.
No Nobel prize fetish.
No imposter syndrome.
No deep desire for flashy publications.
No venting about evil reviewers.
No need to gossip about other scientists.
Only doing good science.
Like a psychopath.
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If you don’t feel stupid doing science you’re not trying hard enough.
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Science is not really happening when the goal is a paper, a presentation, a grant, or any product. It only really happens when the goal is a process of discovery.
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Doing a PhD is - at heart - one long discussion with your mentor. The discussion changes over time - with unexpected turns and ups & downs - but through it all is a pair of people discussing a topic endlessly to make sense of it.
PhD students: choose someone you like to talk to!
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PhD students tend to choose a lab based on the topic, but a creative and supportive environment is more important. If everyone in the lab is miserable, you will probably be miserable there too; and if they are happy and thriving, you'll also likely feel good about yourself there.
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Out today in
@NatureBiotech
! PhD students & postdocs: there's a trick – overlooked and underused – for having new ideas in the creative process. Talk science 1 on 1 with a science buddy that you trust and think of it as an improvisation. …
@MartinJLercher
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How did we lose our tail? A simple question.. but it wasn't really asked before! We discovered a plausible scenario for the genetic mechanism that led to tail loss. Amazing that such a big change may have been caused by such a small genetic event.
@BoXia7
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A central problem in science today is that scientists are encouraged by the system to become just managers; meaning the vast majority of the scientific process is handled solely by grad students, postdocs, & research scientists without much input from the principal investigators.
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The difference between doing a project and presenting it. An observation can lead to many avenues of explorations before focus turns to a specific discovery. Presenting it, in a talk / paper, follows inversely, with broad perspectives coming before & after the specific discovery.
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When looking for a mentor, remember that a career in science is a 1000 times easier if you have a mentor who will - time after time - make the phone calls, write the letters, and enable opportunities for you.. Be sure to choose a mentor you can easily imagine doing that for you.
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Knowing how to give a good talk is a crucial skill to have, but it's mostly not formally taught very well. Here's a 🧵on my strategy for how to prepare for the presentation, actually present it, and then answer the questions.
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The night before my talk at a conference last week, I decided to make it a chalk talk, instead of using my slides. Not being tied down to slides allowed me to jump around as questions came up & our discussion led to new insights. Why did we let PowerPoint take over our meetings?
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It’s a lonely job, leading a research group (professor, principal investigator, group leader – whatever you call it). You talk all day with everyone, but you’re mostly alone with the doubts and risks of the biggest decisions. Doesn’t have to be this way and I’d love to change it.
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Science is unbearable if you hold off on celebrating until the publication of a big paper. The more we enjoy the process, the happier we are..
Celebrate the interesting group meeting, the preparation of a new presentation, the new technique, & the progress our friends are making.
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Here are my 12 guidelines for data exploration and analysis with the right attitude for discovery:
1. You never really finish analyzing a dataset. You just decide to stop and move on at some point, leaving some things undiscovered. 🧵
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The postdoc stage was the hardest for me. Even with the best mentors, the stress from the uncertainty and the self-doubt is very real. Hang in there postdocs.
#postdocappreciationweek
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It is not well appreciated, but the truth is that one never really finishes to analyze a dataset. You just decide to stop and move on at some point, leaving some things undiscovered.
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Our paper is out today in
@Nature
! Imagine getting this plot when studying single-cell data of growing bacteria! Could it be the cell cycle?! We found that a gene’s response to its replication reveals gene regulation on a genomic scale.
@AndrewPountain
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Our opinion piece is out today, "The origin of novel traits in cancer"! Do the phenotypes come first and only later are they locked in by genetic or epigenetic changes? Insights from evolutionary biology are super useful for understanding cancer!
#S_Frank
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In today's
@Nature
, a study shows that remote teams produce fewer breakthroughs! Disruptive science is more likely to come from groups working in close collaboration. 'Night science' discussions may require the kind of energy that's communicated in person.
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Unpopular opinion: the peer review process does significantly improve the final work (though it is inevitably very long and super frustrating).
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We need to have a ‘code of conduct’ for reviewing manuscripts, like (1) if you say that something is not novel then provide the reference. (2) If you propose an experiment, state precisely to which claim it is crucial. (3) If you want to say something nasty then sign your name.
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We should be funding scientists, not projects: grants to individual scientists should be the norm. Also, ideally we would fund scientists only based on their previous work (the best predictor of more good work - not a research proposal) and just trust them to do good science.
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Do you think you would you have discovered a gorilla hiding in plain sight in your data? We found that you are 5 times less likely to do so if you have a specific hypothesis in mind.
*A hypothesis is a liability*
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The notion of ‘genius’ is toxic in academia because it suggests that we either have it or we don’t. Dedicated long-term effort is what’s really required to develop an intuition for a problem. The so-called ‘genius’ may make it look effortless but you can be sure it was hard work.
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Future grad students: if you’re really interested in science, you will go to any university that accepts you (forgetting about any rejections from the prestigious ones) and you will do great science there and you will make our world better.
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Graduate students: don’t fall for the myth of the genius. It’s all hard work in science, no matter how some people try to make it look easy.
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Learning how to “read” the genome is a basic skill for all biologists. As an introduction, here’s a 🧵 about using the genome browser to make a discovery about how we lost our tails. All you need is your 'thinking eye'! (1/13)
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Rules of academia:
Questions are more important than facts
Answers are temporary
Models are provisional
Failure happens a lot
Patience is a requirement
When you’re lucky, hopefully you realize it
Things don’t unfold linearly
If there’s free food, get there early
—Stuart Firestein
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PhD students: it’s a waste to just try to impress your committee at the meeting. Bring them problems, ask for suggestions, and generally think of it as a session in which new ideas can emerge.
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Capitalism in science leads to scientists constantly writing grants instead of focusing on the problem.
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Otto Warburg's grant application from 1921 is just one sentence – “I require 10,000 marks” – and it was fully funded.
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Professors: we must start teaching creativity to PhD students and postdocs! If you are interested in leading a course about the creative scientific process at your university or institute, here is the material we've put together to help you get started.
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It's easy to make fun of basic science. It seems ridiculous to study how cone snails hunt their prey. But actually it led to the discovery of pain medication: a peptide from their venom relieves pain but doesn't paralyze us, as we use a calcium channel differently from fish.💪🧪
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Reviewers should appreciate that good papers often lead to more questions than they answer. The fact that not everything that emerges from a single paper is followed up on should not reduce the reviewer's excitement; it should be seen as a mark of the work's impact.
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Scientists-in-training: find the mentor that is right for you. Here are my guidelines for how to do that 🧵
1. Make sure to choose a mentor who will be deeply committed to your career; someone who will continue advising and supporting you well after your time working together.
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Nothing in Physiology or Medicine makes sense except in the light of evolution.
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New paper! It’s absolutely wild what you see when studying bacteria using single-cell RNA-Seq! Unlike in eukaryotes, we found a genome-scale pattern of correlations among genes showing a strong dependency on global chromosomal locations.
@AndrewPountain
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Learning how to give a good talk is crucial, but we don't teach it as much as we should. Here are the suggestions I give my student about the right kind of preparation, execution, and question-answering approach.
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Postdocs: You will pay a price for switching fields, but you can more than make up for that with the ability to recognize a hidden connection to spark a discovery (cancer -> development; immunology -> evolution; genetics -> physics..).
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Teams composed of just a few people are more likely to produce highly novel (disruptive) work, while larger teams may be best for going big and developing an idea. This notion is supported by classic work by Lingfei Wu,
@dashunwang
, and
@profjamesevans
.
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To the many PhD students starting this month: choosing a mentoring lab - which is THE crucial decision - should be made based on the atmosphere in the lab, the attention you will get from the mentor, what they can teach you, funding, and the lab’s topic, probably in that order.
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Most of academia is by now so distracted by grantsmanship, publishing, and administration they no longer even seen it as a distraction.
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Paper is finally out in
@NatureGenet
! "Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment"
Check out our catalog of conserved cancer cell states defined by scRNA-Seq & ST. Congrats
@BarkleyDalia
!
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A notable scientist accused my team yesterday of being ignorant in biology or not actually believing what we are proposing in the tail manuscript. They make interesting points but starting with insults is distracting and not constructive. A few points..
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It’s funny how those years without publications look bad on the CV, but were actually the ones with the most scientific progress.
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Doing science is hard, so everything else needs to be easy.
Choose a lab where the personal side is supportive with good communication.
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‘In 20 years there will be no bioinformatics; it will just be called biology’ - Charles DeLisi (my PhD advisor, as quoted in my thesis). That was nearly 20 years ago, and I think he was right. Grad students and postdocs in particular know they need to be computational now too.
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The hardest thing in academia is the postdoc stage. So while it seems obvious, it’s still worth repeating:
PIs, remember to give your postdocs daily encouragement and help transitioning to their next career step.
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The secret to staying calm as you prepare to give a good presentation is to remind yourself that you want to explain, not to impress.
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Writing a good grant proposal involves both creative ('night science') and executive ('day science') aspects that are important to distinguish. Here's a 🧵on my strategy for deciding what to propose and the process of actually putting the grant together.
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Standard advice to:
PhD students - focus on your advisor’s questions.
Postdocs - it’s too risky to search for a new question.
Junior faculty - stay conservative until you get tenure.
But to remain engaged in science, be sure to nurture your creativity at every career stage.
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Choose the mentor that has the time to talk with you and who energizes you on a weekly basis.
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😯 François Jacob (co-discoverer of gene regulation) asked by Lucy Shapiro (Stanford):
"It's always been hypothesis-driven research [..] but a new way is looking at vast amounts of data and not asking a question, just seeing if it give you a pattern."
Jacob: "It’s very boring.."
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A common way to ruin your project is to skip doing a series of pilots before the big expensive experiment. Pilots help you work out the problems and prevent the creation of impossible-to-analyze datasets. Published papers often don't discuss pilots, encouraging us to do the same.
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What does a mentor advise a mentee to do on the weekends? I encourage my lab members to rest but it’s a bit hypocritical because when I was at their stage I worked on the days off (and still do, kind of..). Maybe the best thing is to just make sure there's no expectation to work.
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Top 10 misconceptions about the situation in Israel:
1. ‘Standing by Israel’ means you are anti-Palestinian. (You can both unequivocally condemn this attack & support Palestinian rights.)
2. Hamas wants to ‘Free Palestine’. (It wants Jews dead; see their charter's Article 7.)
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To increase our innovative thinking we need to allow time for the creative process: using analogies, finding new questions, embracing contradictions, importing/exporting ideas, improvising, exploring the data & puzzle-switch.
Joint work w/
@MartinJLercher
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PhD students and postdocs are the most likely to make the key discovery in a field, because they can look with fresh eyes at well-known observations and understand for the first time what they actually mean.
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Ever hear that ‘necessity is the mother of invention’? In our new work, we found that it’s also true for cancer cells as they continuously adapt to drug treatments. We call it a ‘resistance continuum’ that's dependent on treatment history.
@Gustavo_SFranca
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In today's Cell, we propose a “developmental constraint” model whereby cancer cell state plasticity is restricted by the organism’s developmental map to access progenitor-like states and differentiated-like states of adjacent lineages.🧵⬇️
@AyushiPatel3994
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A secret superpower of a lab with more than one research topic is that group meetings are a safe space for naive questions - because there are many ‘outsiders’ - and a big idea tends to start out as a naive question.
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A big part of the scientific process is just having someone to talk to. If you can spare a few minutes, ask a colleague what they're working on..
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🔥Check out our new paper🔥
Make Science Disruptive Again! All graduate programs should teach the CREATIVE SCIENTIFIC PROCESS to help change the research system and increase the disruptiveness of science projects.
@MartinJLercher
@NatureBiotech
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The revolution comes to science when we finally dethrone the hypothesis-driven mode as the only respectable form of scientific inquiry for grant and thesis proposals.
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People will try to label you as though it’s the most natural thing: ‘are you an immunologist, a microbiologist, or a computational biologist?’
Don’t fall for that. A label may limit your opportunities to do basic research, and find new things regardless of human-made divisions.
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Prospective postdocs: make sure to choose a mentor who will be deeply committed to your career; someone who will continue to advise and support you well after your time in their lab. You could say that the postdoc-mentor relationship is the closest thing to marriage in academia!
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Jews this week have had to do 2 things simultaneously: process the horrors of the attack and deal with anti-Israel/antisemitic sentiments plus the painful silence of most folks. It's been difficult but also frees us from any illusions we might have had on our status in the world
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It is not the dissertation, tenure or retirement, but finding a good collaborator which is truly the important event in your career.
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Sperm cells express nearly all genes - a well-known yet mysterious observation. In our new paper, we hypothesize ‘transcriptional scanning’ where expression is coupled globally for DNA repair and even modulates gene evolution rates.
@boxia
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My rules for academia: 1. there are many paths to success, look for your own, 2. if the project excites you, do it; if it doesn’t, don’t. 3. let the project change, that’s what it’s supposed to do, 4. review the work of as you’d want to be reviewed, 5. one sentence, one idea.
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If you’re not embarrassed by your first bioRxiv version of the paper, then you’ve waited too long.
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Had a potentially life-changing experience yesterday listening to a talk by
@BobFarese
and
@TobiWalther
and realizing the benefits of having the kind a scientific partnership that comes with having a joint lab. I’m thinking now that I would really love to do that!
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When I was a postdoc, I heard about a lab where the professor & two postdocs talked all day in front of a blackboard for months. Then they'd go into the lab to do the experiment they settled on, which would lead to a big discovery. Then they'd repeat that process again & again..
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Can not studying popular genes cost you your career?!
Check out how the probability of a junior scientist to transition to a principal investigator is lower if the genes they research are less studied. The overall decreasing probability is also really depressing! (from Fig. S10)
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Real science:
1. Is not correlated with the amount of funding
2. Progresses slowly, usually taking many years
3. Leads to more questions than it answers
4. Advances when we disengage & in improvisational discussions
5. Is too important a thing to be done in a non-playful way
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Starting PhD students and postdocs should be advised against working on a specific project right away. It’s better to first explore opportunities with colleagues & to be open to an extended process of improvising ideas. It may seem like a waste of time, but it’s actually crucial.
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Here’s one piece of advice to the newly minted assistant professors: when setting up the group meetings do it so that you yourself are also in the rotation. I still present regularly in our lab meetings and I feel it helps a lot to create an egalitarian and motivated atmosphere.
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There’s this unfortunate myth in science that the head of the lab alone controls its culture. In reality, all the members do and so each person should realize that they bring their own values, attitudes, and spirit for how things should be and that this does matter quite a bit.
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New paper🔥! How do macrophages respond to bacterial infection? We identify distinct states with a highly inflammatory state composed of sequentially expressed gene modules and dynamics that depend on the pathogen, infection length, & toxins.🧵
@CellReports
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Science Twitter: the last 19 days were a living hell for our Israeli colleagues. Their loved ones have been brutally murdered in their homes, raped and kidnapped. They spend hours sheltering from bombings. They feel scared, angry, & isolated. This is the time to show our support.
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What advice do editors have for authors on the process of publishing? Barbara Cheifet - Chief Editor
@NatureBiotech
- came to talk with us yesterday and here is her top 10 list (with permission):
1. Aim high, but also be realistic about where your paper could be accepted.
🧵⬇️
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Are computational biologists the drivers of research? 7 years ago I co-wrote an editorial about how computational biologists are no longer just supportive, but are now running the show. Today I would write how every biologist should also be computational.
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What are the principles of intra-tumor heterogeneity? In our new work, we studied 15 cancer types using scRNA-Seq, spatial transcriptomics and CODEX to propose a unified catalog of gene modules that underpin recurrent cancer cell states.
@BarkleyDalia
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I want to tell you a story about a recent discovery that we made in the lab, because we often argue here whether it’s the data or the hypothesis that comes first. In the case of this discovery, it was definitely the data that showed us something that we completely didn't expect.
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Novelty needs time. For the first 3 years after publication, a highly novel paper is less likely to be cited than a relatively non-novel paper. But after 15 years, they are 60% more likely to be highly cited. Don't let the short-term view discourage risky research!
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You can’t admit this in a grant or a paper, but the way to begin a project is just by starting to do something even though it may not seem like a novel direction. The important thing is to start to make observations and the novel ideas will follow.
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Grad students: have you discovered Uri Alon’s classic ‘How To Choose a Good Scientific Problem’ yet?
@UriAlonWeizmann
discusses self expression, taking your time when choosing a project, and the support required for the exploration of new directions.
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Don’t wait for the perfect dataset; you’ll wait forever. Explore right away the good-enough dataset.
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(True story; wish it was more common)
Junior faculty: None of my proposals are being funded. I’m worried..
Dept. Chair: Why not take a 6 month rest from grant writing?
Junior faculty: But I need to get a grant..
Chair: Don’t worry, I’ve got your back. Just focus on the science.
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For a good training in science, aspire to be experimental, computational, & theoretical. Without being experimental, it’s hard to have the data you need. Without being computational, it’s hard to interpret your own data. Without being theoretical, it’s hard to have new ideas.
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