Sad news: Andreas Doncic

I have unfortunately learned today that our lab's collaborator, Andreas Doncic, has passed away after a fatal traffic accident in Dallas, Texas. Andreas was a group leader at UT Southwestern Medical Center and his passion lay in learning how cells make decisions. Our labs recently collaborated and published a project together and were looking forward to future potential joint efforts.

When he visited our lab last year, I remember Andreas being one of the warmest and funniest scientists I've met. Andreas' passing is a great loss for his family and the scientific community as well. We keep his wife Kei and children Maya and Alexander in our thoughts. Thank you Andreas, and I'm sorry we must say good bye so soon.

A collection page has been set up towards the college fund for Andreas' children:

Fabien's paper is published!

Our post-doc, Fabien Moretto, has published an article in Nature Communications! Congrats Fabien, this paper's been a long time coming!

A regulatory circuit of two lncRNAs and a master regulator directs cell fate in yeast

This work was done in collaboration with the lab of Andreas Doncic at UT Southwestern Medical Center.

Fabien and the other co-authors showed that a master regulator gene orchestrates transcription of two contiguous long non-coding RNAs (lncRNAs) within its own promoter. 

IME1 is the master regulator for the yeast cell fate's decision to undergo a binary cell fate decision - to sporulate or not.  In an unusual regulatory circuit involving two lncRNAs, several transcription factors, and local chromatin changes, IME1 can stimulate its own promoter. This local stimulation promotes IME1 expression and increases the efficiency of sporulation. By tracking the accumulation of IME1 in cells where the regulatory circuit was perturbed, they formulated a simple mathematical model to simulate the feedback loop. This circuit might have evolved to tightly control expression of the master regulator in response to prolonged starvation or transient nutrient deprivation.

I particularly like the single-molecule RNA FISH analysis of this paper, and we've managed to integrate some of it into my project as well. We've got a nice story in the works!

Two new papers from our lab!

Wow! My good friend Minghao, in collaboration with Elçin Ünal at the University of California, Berkeley, has published not one, but two articles in eLife! Read more below.

Transcription of a 5' extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter

Our groups elucidated the transcriptional interference mechanism from a 5' extended long undecoded NDC80 transcript isoform upon its own mRNA. This effectively promotes dynamic changes in gene expression during cell differentiation.

Kinetochore inactivation by expression of a repressive mRNA

Our labs demonstrated how transcriptional and translational inhibitory mechanisms are integrated during meiosis to temporally restrict kinetochore function. The 5' extended long undecoded NDC80 transcript isoform carries the canonical mRNA sequence, but directly causes gene repression instead.

RIP Bernie Kully

I've just learned that my former teacher and coach at St. Thomas More Collegiate, Bernie Kully, has passed away from cancer. My sincere condolences to everyone within the STMC community. Mr. Kully was a selfless, caring, and kind man who gave everything he had to his students and the school community - he did things the right way. He'll be very much missed by all of us.


My Top 10 Films of All Time

It's always important to take some time off work! Don't let anybody tell you otherwise.

Here are my top 10 films of all time, with some honourable mentions.

  1. The Dark Knight
  2. Porco Rosso
  3. The Incredibles
  4. Spirited Away
  5. Inception
  6. Return of the Jedi
  7. The Departed
  8. Monty Python's Life of Brian
  9. Princess Mononoke
  10. Forrest Gump

Other favourites:

  • The Pianist
  • Schindler's List
  • Princess Mononoke
  • Kiki's Delivery Service
  • Grave of the Fireflies
  • The Wind Rises
  • When Marnie was There
  • Good Will Hunting
  • Pirates of the Caribbean
  • Coach Carter
  • Ratatouille
  • Monty Python and the Holy Grail
  • Monsters, Inc.
  • Tangled
  • Big Hero 6
  • Game of Thrones*

And there's a couple which, shamefully, I've never watched but expect to make the top 10 list:

  • The Godfather
  • The Shawshank Redemption

Learning to talk for a living

Science is getting harder, more complex, and has more influence on society. Even though I'd like to busy myself and bury myself in experiments, I'd be letting down the generations of scientists who came before me if I didn't explain to the public why we're banging our heads on desks.

Recently, I've found that I have to give the "elevator pitch" to a lot of people I meet for the first time, to introduce myself and what I do every day. Usually it's just the same listless, blanket statements, but I try my best to make baker's yeast relatable to people. I don't expect everyone to love molecular biology, nor should I expect to. However, in the wake of Brexit and the Trump administration's short-sighted, or even draconian, policies that are hurting science, I think scientists do have a duty to explain that our work saves lives, improves health, prevents diseases, and makes knowledge. Frankly, it's selfish to let obtuse, impetuous politicians and inconsiderate, bigoted, angry people take that away from future generations.

For me, it's about sacrificing and being part of something bigger than myself to make people's lives better. That's it. And that's what it'll always be about.

A Sad Day for America, the World, and Human Decency

Clearly, the American electorate spoke last night. And clearly, they decided that a liar, a misogynist, a xenophobe, a bigot, an idiot, a tax avoider, a demagogue, and a despicable human being who has bragged about sexual assaults on women was more palatable than having their first female President.

It's no secret that tangible, feasible, effective, and visible change is needed to bridge growing socio-economic and cultural divides in the Western world. But a growing xenophobia and fear of change warrants political action and enactment of democracy. It does not license what is supposedly a decent, resilient, honest, earnest, and respectful nation of over 300 million people to present a man without morals or conscience as their representative, their leader, their face to the world.

I'm deeply disappointed that both liberal and conservative voters failed to see past the fear stemming from many places, and sought to address this by granting access to the codes to authorise a nuclear attack to an imbecile. That's not the United States of America I got to know, growing up. Those are not the welcoming, decent, kind, selfless, and inspiring American people I met.

To those who believe in hope, in decency, in inclusion, in national pride, in equality, and in respect: We need to continue fighting for the important principles we believe in, with every fibre of our beings. Because, sometimes the easiest thing to do is not the right thing to do, but will be worth it for our generation and for our kids' and grandkids' generations. These social, cultural, political, and economic issues are deserving of our best.

Do not go gentle into that good night.


I'm quite saddened today to hear of the passing of someone I used to coach basketball with back in Vancouver, Eric Ming. He was simply a truly inspirational mentor, role model, and coach to his team, and taught me a lot about toughness, mental fortitude, and purpose. He unfortunately lost an ongoing battle with leukemia recently.

It has definitely made me think about my motivations for doing research. Clearly my work is on the very fundamentals of biology, with the hope that a greater understanding of conserved mechanisms will provide a foundation for future discoveries, technologies, and therapies. On the other hand, this account encourages some thought on the merits and perhaps more personal motivations in therapeutic research. I'd like nothing more than to help others through my work. My thoughts on this are still unclear, but I'm sure I'll take some time to consider things while paying my respects to my my fellow basketball coach.

Rest in peace, Eric, and thank you.

Two more new lab papers!

Minghao and Fabien from our Cell Fate and Gene Regulation Laboratory at the Francis Crick Institute have published, respectively, new papers on how temporal control of a master regulator (IME1) drives sporulation in budding yeast, and how transcription of the mating-type regulated lncRNA IRT1 (which helps control IME1 transcription) is governed by the TORC1 and PKA signaling pathways. Definitely a couple of good reads, and more exciting stuff in the works!

Temporal expression of a master regulator drives synchronous sporulation in budding yeast

Minghao Chia and Folkert J. van Werven

Transcription of the mating-type-regulated lncRNA IRT1 is governed by TORC1 and PKA

Fabien Moretto and Folkert J. van Werven

Our Lab's First Paper!

Our lab, the Cell Fate and Gene Regulation Lab led by Folkert van Werven at the Francis Crick Institute, has published our first paper! It's been a long time coming, but it must be fantastic for Folkert, Fabien, Gianpiero, and our collaborators at MIT as well.

Nutrient Control of Yeast Gametogenesis is Mediated by TORC1, PKA and Energy Availability

Hilla Weidberg, Fabien Moretto, Gianpiero Spedale, Angelika Amon, Folkert J. van Werven

Further information is available below:

The Road Not Taken

Two roads diverged in a yellow wood,
And sorry I could not travel both
And be one traveler, long I stood
And looked down one as far as I could
To where it bent in the undergrowth;
Then took the other, as just as fair,
And having perhaps the better claim,
Because it was grassy and wanted wear;
Though as for that the passing there
Had worn them really about the same,
And both that morning equally lay
In leaves no step had trodden black.
Oh, I kept the first for another day!
Yet knowing how way leads on to way,
I doubted if I should ever come back.
I shall be telling this with a sigh
Somewhere ages and ages hence:
Two roads diverged in a wood, and I—
I took the one less traveled by,
And that has made all the difference.

Robert Frost

The Fig Tree

I saw my life branching out before me like the green fig tree in the story.  From the tip of every branch, like a fat purple fig, a wonderful future beckoned and winked. 
One fig was a husband and a happy home and children, and another fig was a famous poet and another fig was a brilliant professor, and another fig was Ee Gee, the amazing editor, and another fig was Europe and Africa and South America, and another fig was Constantin and Socrates and Attila and a pack of other lovers with queer names and offbeat professions, and another fig was an Olympic lady crew champion, and beyond and above these figs were many more figs I couldn't quite make out. 
I saw myself sitting in the crotch of this fig tree, starving to death, just because I couldn't make up my mind which of the figs I would choose. 
I wanted each and every one of them, but choosing one meant losing all the rest, and, as I sat there, unable to decide, the figs began to wrinkle and go black, and, one by one, they plopped to the ground at my feet.

Sylvia Plath, The Bell Jar

Research Directions and Negative Results

In other words, my thesis committee meeting to upgrade from MPhil to PhD is coming up soon!

I've had a long string of technically and biologically sound, but negative results recently. So that means I won't present any publication-ready, pioneering data or results yet. We picked a few research directions that looked initially promising, and some worked great and some didn't work at all. Oh well, c'est la vie! (That's the PC version, my labmates usually hear me mutter less polite words under my breath when I see the data).

At this point, I'm not ecstatic, but still comfortable with presenting negative data. In many respects, it can be as informative as positive data as well. Nobody's done this before, and troubleshooting is hard work! I think that getting experiments to work well and consistently doesn't get enough credit, sometimes, in biology.

For now, I think the best thing is to keep my head down and toiling away at this project. One little step at a time! We've got some nice RNA-seq data that I have to annotate. Manually. For over 100 genes.

I'll leave you with a couple of my favourite excerpts / poems above:

The Fig Tree from Sylvia Plath's "The Bell Jar"

The Road Not Taken by Robert Frost

"Hello. My name is Inigo Montoya. You killed my father. Preprare to die!"

In other words, En Garde!

I've recently picked up fencing, and I'm really enjoying learning this complex, exciting, and wonderful sport! There are many reasons why I enjoy fencing, but I think that it appeals to many of the same pars of my brain that science happens to as well.

First things first - I like to fence épée, and a bit of foil as well. They are both weapons with which you score points by "poking somebody with the pointy end". For the sake of brevity, I will limit this to my favourite weapon, épée.

Fencing is one of the few sports where one must be 100% focused - before, during, and after a bout. There's very little else you can think about when somebody is trying to hit you with a long piece of metal. It's a very nice change from the monotony of a treadmill, spin bike, or rowing machine. I normally consider and visualise the technical parries, feints, and attacks I plan to use, but most of the time, I try to study and analyse my opponents. I quite enjoy the mental exercise of breaking down their tendencies, strengths and weaknesses, and coming up with creative solutions to work around their approaches.

It's been said that fencing is a form of "physical chess". I understand that it's a sport of trying to out-think and out-feint your opponent, but I'd argue that it's a lot more difficult as well - simply due to the inherent speed of the bouts and the technical difficulty in executing the motions.

It'a also immensely satisfying to try something you've imagined in fight, and have it work exactly the way you want it to. Or, when you come up with a successful parry-riposte simply by reacting instinctively and creatively - watching top foilists and épéeists compete is like enjoying a symphony of self-expression.

Finally, this is a sport steeped in history, tradition, and respect. I like being a part of that a lot.

All that being said, there's nothing more cathartic at the end of a long day in the lab than poking your friends with pointy sticks.

Tetrad Dissection

Yeast biologists will know this. You have a love-hate relationship with tetrad dissection. On one hand - it's the activity that requires 100% of your mental focus, and you can escape your busy day for a while. On the other hand, it's 9 PM on a Friday night and you have 6 full plates still to go. 

Basically: yeast can exist with one or two copies of their genomes. When 2 haploid (1 genome copy) cells of opposite mating types meet, they form shmoos and can combine their nuclear contents to form a diploid cell (2 genome copies). When diploid yeasts are starved, they undergo gametogenesis or sporulation and form 4 spores, each with 1 haploid genome each.

Fortunately, the good chaps at the Carlsberg Laboratories whom I've mentioned before - Lindgren & Winde - developed techniques to analyse the recombination and segregation of genes in haploid & diploid cells.

In practice, this means I pick apart tiny yeast spores with a fine glass needle.

Imagine this: you have a plate full of gummy bears on a surface that has the same stickiness you might find on a sketchy nightclub floor. Most of the gummy bears are by themselves, but some are stuck together in clusters of 4. You are suspended upside-down from the ceiling, and can only manipulate the gummy bears with a meter-long stick. Your task is to pick up a cluster of 4, break it apart into individual bears, and place each individual bear on a pre-determined grid location. Now do that 19 more times for 1 plate, and complete the whole routine 5 more times because you've been putting this off for a while.

My record is 22m 15s for a full plate (20 tetrads). I'm looking forward to seeing how much quicker I'll be at the end of these 4 years!

Friday Afternoon Lab Playlist

For those times when you have a million tasks to complete, all of which require your immediate attention. It's a bit eclectic, but I hope there's something for all tastes.

Please enjoy!

  1. Piano Man - Billy Joel
  2. Only The Good Die Young - Billy Joel
  3. And So It Goes - Billy Joel
  4. New York State of Mind - Billy Joel
  5. We Didn't Start the Fire - Billy Joel
  6. Starman - David Bowie
  7. Space Oddity - David Bowie
  8. Heroes - David Bowie
  9. Rebel Rebel - David Bowie
  10. Changes - David Bowie
  11. Tiny Dancer - Elton John
  12. Rocket Man - Elton John
  13. My Way - Frank Sinatra
  14. Born to Run - Bruce Springsteen
  15. Dancing in the Dark - Bruce Springsteen
  16. Le Temps de Cerises - Clément & Renard
  17. Nocturne Op. 9 No. 2 - Chopin
  18. Man in the Mirror - Michael Jackson
  19. La Vie en Rose - Louis Armstrong
  20. The Times They Are A Changin' - Bob Dylan
  21. Try a Little Tenderness - Otis Redding
  22. All the Faces - Creed Bratton
  23. Wild Horses - The Rolling Stones
  24. To Make You Feel My Love - Billy Joel & Bob Dylan
  25. What a Wonderful World - Louis Armstrong
  26. Old Kentucky Blues - Louis Armstrong
  27. These Foolish Things - Billie Holiday
  28. Stand By Me - Ben E. King
  29. Leaving on a Jet Plane - John Denver
  30. Take Me Home, Country Roads - John Denver
  31. Georgia On My Mind - Ray Charles
  32. Fly Me To The Moon - Nat King Cole
  33. Ain't No Mountain High Enough - Marvin Gaye
  34. My Way - Frank Sinatra
  35. Young and Beautiful - Lana Del Rey
  36. Born to Die - Lana Del Rey
  37. Shake It Out - Florence and the Machine
  38. Fortunate Son - CCR
  39. I Still Haven't Found What I'm Looking For - U2
  40. Losing My Religion - R.E.M.
  41. If I Ain't Got You - Alicia Keys
  42. Doo-Wop (That Thing) - Lauryn Hill
  43. Bohemian Rhapsody - Queen
  44. Don't Stop Me Now - Queen
  45. Somebody to Love - Queen
  46. Sweet Home Alabama - Lynyrd Skynyrd
  47. Live Like You Were Dying - Tim McGraw
  48. Life is a Highway - Tom Cochrane
  49. Fix You - Coldplay
  50. Somewhere Only We Know - Keane

"So...What Do You Actually Do?"

First things first - I follow a column called "Experimental Error" written by Adam Ruben at Science Careers, and it's excellent. I highly recommend that you read it. 

Second disclosure: I don't see myself as an insightful, brilliant, theorist who can explain biological phenomena after meditative thought. I don't know many who are.

I'm more of a Nespresso-fuelled nerd who amazes himself with his stupidity on a daily basis, but happens to be kind of practical and enjoys science partly because it feels like cooking (and vice versa).

His most recent post, "Why we need another Einstein", makes some very insightful and salient points on the greater public's perception of scientists. I believe it's absolutely clear that we who have the privilege to do science, have a duty to share some of it with all strata of the public. This is because scientific and societal progress are intertwined and interdependent - especially in today's day and age.

However, not all of us are as enthusiastic as Bill Nye, as talented at public engagement as Neil DeGrasse Tyson, or as brilliant as Stephen Hawking. And not all members of the public are equally interested in science - that, I'm thankful for!

So, when we finally get the chance to escape from the lab, awkwardly nursing a drink at the pub with friends or strangers - how do we answer the question, "So, what do you do?"

And, how do we explain this research project that consumes our working days (and nights, and weekends sometimes) with enough tact to avoid the intricacies of tetrad dissection or that insightful Molecular Cell paper you read this week?

I'll use a personal anecdote. One of my many hidden talents is the ability to talk science at people until they die of boredom. This is a very niche talent, and I'm sure it'll come in handy someday. However, it's not very useful for most social situations. How do I try to make people who don't usually discuss science partly understand what I do?

Science has been presented as an abstract profession in popular culture; this has created a detachment from the lay population, that can be dismissive at times. That's partly our own fault, too. I mean, when someone describes themselves as a brave firefighter, a talented baker, or a promising athlete - you usually know exactly what they do. In fact, you might think that you could probably do their job as well, and perhaps even do it well.

But - when it comes to the laudable career of scientific research, explaining why your Western blots are giving contradictory results is not a suitable topic to converse about. That's because conversations require both parties to relate to the topic in some way, and the exchange tends to break down otherwise (sounds a lot like some of our fascinating departmental seminars, which I usually attend for the free lunch).

I like to lead others in with a Fun Science Fact - that I would not have a day job if not for Øjvind Winge and the brilliant pioneers at the Carlsberg Laboratory in Copenhagen. The methods and yeast strains originally developed to make your pint taste "hoppy" or "full" have contributed to some of the most seminal discoveries in molecular biology in the past century (and continue to do so). I mean, how cool is that!

I think, what we should do, is actually show people that science is cool. And that regular people, not Sheldons, do science. I think Andy Weir, Ridley Scott, and Matt Damon have done impeccably in this endeavour with The Martian. (Read the book, people!)

Mark Watney shows that science is actually about educated guesswork, improvising with what you have and making things work, messing around with hazardous chemicals, deftly ignoring false leads, and getting properly stuck into problems to solve them, one by one.

In other words, what do I actually do?

I get to play with expensive equipment and radioactivity, ask and answer questions about the fascinating mechanisms of life itself, and generally science the shit out of things.

I love what I do. I hope that others can understand, at the very least, why I do it.

Types of Lab Protocols, Ranked from Worst to Best

  1. That one protocol you’re sick of doing because it never works and why did I decide to enrol in grad school and I have no data to present at lab meeting tomorrow
  2. Errrr… I haven’t done it yet.
  3. Alternative protocol – ie. “we did it like this in my old lab” (Your supervisor will love this)
  4. Illegible protocol from previous student’s lab book (they have since left science to start a bakery)
  5. Protocol from memory
  6. Verbally Dictated – sketchy at best
  7. Make it up as you go along
  8. “Go look it up”
  9. A protocol that really shouldn’t work, but does.
  10. Post-It note based
  11. Verbally Dictated – detailed
  12. Hyper-organised protocol explicitly stating all reagents and kits with troubleshooting steps*

*pretty much one in a million

My solution is to go electronic. And always, always, ask if you’re unsure!