Archive
Editorial – A Tenured Professor: an Academic Sportsperson successfully gone Professional
Imagine, you just looked through the lens of a microscope. You see only five chromosomes. Not ten, but five. At first you think this must be a mistake, but your postdoc assures you that it is real. There really are only five chromosomes. Your post-doc re-did the experiment and found the same ‘errors’ again. More interestingly, the mutant phenotype your postdoc expected to see was absent. The plants looked normal. As if all of the chromosomes were from a single parent. It daunted on both your postdoc and you that you are looking at a haploid genome. You made a haploid plant. Even better, every now and then one of the offspring will be a homozygous diploid plant. The potential for plant breeding are ridiculous. Now it is theoretically possible to create a mutant of your likings and with a single cross you can have a ‘pure’ mutant plant containing only your phenotype of interest. No need to do a dozens of back-crosses to clean up the background mutations. You have a plant breeding revolution in your hands. Of course this work was published in the top-tier journal Nature. This observation was like winning a gold medal at the olympics.
This is what a success story of a young scientist could look like. Indeed, this is the success story of Simon Chan. His plant breeding revolution in progress was rewarded with a Howard Hughes Medical Institute / Gordon and Betty Moore Foundation (HHMI/GBMF) fellowship at age 37. A success story which would have had many more chapters if he had not died on August 22nd, 2012.
The road Simon took to get to where he ended was a regular one; one almost every professor has taken. After college in New Zealand he went to graduate school (UCSF). He joined a well established lab of Elisabeth Blackburn (would later receive the Nobel Price, the equivalent of being inducted into the Hall of (Science) Fame). After completing his PhD, he moved on to a post-doc position in Steve Jacobsen’s lab at UCLA. After four years of post-doc-ing, Simon applied to and was offered a faculty position at UC Davis. Whereas Simon did one post-doc, many of his pears have taken two or three post-docs before becoming tenured faculty. There are some rare occasions, such as Joe DeRisi at UCSF, where someone becomes a professor directly out of graduate school, skipping the postdoc step all together.
Just about every graduate student today is being trained/mentored by a professor who took this very same route.
[College -> Grad school -> post-doc (-> post-doc (-> post-doc ...)) -> faculty]
This is not the case for your average professional football player, as they are often represented by a manager. Yet their professional mentors are almost always former professional football players.
Does this mean that these rather different people don’t experience very similar problems, such as the potential for great personal gain or in both cases understudied mental health challenges [sport | science].
Life for the average graduate student (or postdoc or professor) is not that straightforward. First of all, doing research can be very expensive. Of course scientists cannot pay for their experiments out of their own pockets. To fund your research you enter the rat race of grant applications, where the odds for getting funded keep dwindling. Getting a fellowship, scholarships, or grant is like being recognized by scouts. It proofs that you are considered a talent worth investing in.
The analogy with professional sports persons is not that far-fetched. Allow me to elaborate. Say you would like to become a professional football player (or soccer if you prefer that term). You start playing football with your friends on the street and once you are between four and six years old, your parents will bring you to the local football club (or FC). Here you will receive your first formal football training and here you will play your first official football matches. It like you are taking science classes and you are partaking in your first science fair. This would hopefully spark your interest in majoring in science and subsequently apply for graduate school.
Once you succeeded at your local football club, you will move to a bigger club that will further your official football training. Many of the biggest clubs in the world have a player development program. For example, Lionel Messi was recruited by River Plate at age 11 and before he was able to start at River Plate, he was picked up by FC Barcelona. Most of us know that today he broke Müller’s record of 85 goals in one season.
Just like Messi, every aspiring young football player dreams of playing at the biggest stages and be part of the biggest league in the world. In science the biggest league is the United States. At this moment, more money is pored in basic research in the US than anywhere else. This means that it would benefit an individual scientist career to do part of its training in the US, as did Simon.
In football, a single event can make or break you career. Being recognized by scouts at an early age can pave your way to Camp Nou, as it did for Messi. Being recognized by an early career award makes you a more attractive up-and-coming scientist. On the other end of the spectrum, a career of a great talent in football can be broken in a single moment, as in literally broken, as it happened to David Busst. Similarly, in science this can happen. One of the most notorious examples is Hwang Woo Suk who claimed to be able to clone embryonic stem cells. Scientific misconduct is the worst possible offense in science. Although it is not known how common this is, most scientists do not quit the rat race because of it. A scientific career tends to end when you try to move up on the academic ladder of success. (This is also the most common reason for prospective professional football-players quite their dreams.)
In both football and science, a fair amount of leeway exists to make ‘errors’. L’enfant terribles such as Eric Cantona or Nigel de Jong are notorious for their antics, yet they both had and have successful careers. In science a retraction could be seen as an ‘error’. Recently, PLoS Pathogens retracted a paper from the DeRisi lab at UCSF. Although I am not familiar what the effects were for the lead author of the retracted paper, Joe DeRisi didn’t suffer from this ‘error’. The value a particular player or scientist is perceived to have in their respective fields helps them maintain their respective edge, as does their legacy. Established players and scientists simply have more leeway for ‘errors’.
This brings us down to luck. Success in either football (or any other sport) or science depend on luck. Without a well established scout defining you as a future star, your odds of playing for AC Milan or Real Madrid, greatly decreases. The same is true for scientists who made a well-talked about scientific discovery. Of course, you need to be talented and you need to work hard, very hard. Luck is the one factor that no football player or scientist can control. For a scientist just to keep up with the literature, you have to read at least one article per day. That would be the equivalent of say 350 articles per year or 1750 articles at the end of a 5 year PhD. Add to this three-to-five years of post-doc, you could have read roughly between 2080 to 3500 articles before you start your faculty position you aimed to reach. Devoting many hours to your trait helps increase the odds of becoming lucky, but that comes at a cost: less time for non-football or non-science related things.
To be a successful professional football player of scientist, you need to show great perseverance and resilience. Do you have the perseverance and resilience to become the next top scientist?
Stay Calm and Carry On.
P.S. Advised reading: Chapters 2, 7 and 10 from How Economics Shapes Science by Paula Stephan. In Chapter 2, Stephan compares tenured faculty with professional sports persons.
Top 10 Best Things To Know As An Incoming Graduate Student
Top 10 Best Things To Know As An Incoming Graduate Student
1. Cite EVERYTHING, especially if it was written by your PI. And make sure you read all those papers as well.
2. Remember that it’s better to be called “roton” than rotten.
3. Establish study groups early, and ask questions if you’re confused.
4. Don’t forget to eat, sleep, and occasionally have some fun (outside of lab)
5. Become friends with the lab technician- they know where everything is and how to operate it.
6. Liquid nitrogen is cold, very cold. Likewise, Bunsen burners are hot, very hot.
7. Go out to lunch with your fellow first years- they understand best what you are going through, and 20 years from now they might be reviewing your papers.
8. Don’t be afraid of cockroaches, dead mice, or Drosophila. They’ll turn up in the most unlikely places.
9. If you don’t like a lab after 5 weeks, you are definitely not going to like it after 5 years.
10. Get organized- keep a calendar and a list of things to do. 5 years feels like all the time in the world, but goes by incredibly fast.
Good luck first years
-BMCDB Bloggers
Tips for riding your bike around UC Davis
This first week of all the students being back in Davis is an exciting time but, also a hazardous time. The main danger being, riding your bike in a sea of inexperienced freshmen who are unfamiliar with the rules of the road and the responsibilities of riding a bike in Davis. Here are some tips to help avoid an embarrassing, costly and potentially harmful situation on your bike.
First tip: Get familiar with the laws/rules for riding a bike. Cops in Davis will pull you over and ticket you on your bike for: running a stop sign or red light, not using your hand to signal, riding with both headphones in (one is alright), riding inebriated (can lead to losing your drivers license) or otherwise irresponsibly/dangerously, and I think most importantly – for not having a bike light at night. A strong front light, back light, and ideally white or reflective clothing are strongly recommended while biking at night. Also, be familiar with the signs and be careful not to ride your bike in certain areas where it is forbidden (the MU and in certain sections of the Arboretum).
Second Tip: Pay attention while entering/exiting rotaries on campus! Most sensible people are familiar with the rotaries, but unfortunately most freshman are not very sensible. Technically the riders in the rotary have the right of way. Bikes entering the rotary must yield to bikes already in the rotary however, do not count on other riders to adhere to this rule. Many people will just bike right into a rotary without looking, so just be aware of this. When exiting the rotary it is never a bad idea to signal, and check over your shoulder that you will not hit another rider as you turn out of the rotary. Also be wary of actual traffic in the rotaries, buses, trucks, and cops can cause mass confusion when a high volume of bike traffic is present. Rotaries mishaps account for the majority of collisions and injuries on campus, so just be careful!
Third tip: Don’t be afraid to speak up! While riding around campus, especially around lunch of in between classes you will run into groups of slow moving bikes or people walking in the bike lane. Occasionally you can easily pass them by, but it is often necessary to alert those blocking the way of your presence. Just a quick “On your left/right” can save you from getting nailed by a swerving bike or errant pedestrian. Also very helpful with riders who are unable to ride in a straight line or are completely unaware of their surroundings (be especially aware of Cruiser bikes as they tend to be harder to control).
Davis is a great place to ride a bike, just make sure you do it safely and responsibly. If anyone has any other recommendations or stories please feel free to chime in!
Updates: When walking in a bike lane, remember to walk on the left side so you can see oncoming traffic. It is also a good idea to buy a U-lock, almost any other kind of lock can be easily cut (and there is nothing worse than finishing a long day in lab, and finding out that your bike has been stolen). Also a good idea to register your bike with the campus police for a variety of reasons.
Pro tip: As we transition from Summer/Fall into winter remember that the weather changes dramatically. Equipping yourself with splash guards on your front and rear bike tires can save you from getting an impromtu mud facial next time it rains. Riding your bike in the rain is not that bad, as long as you have the right equipment. Getting a solid rain jacket, rain pants, and a pair of water resistant gloves will make you much happier when you arrive at your destination.
Happy Riding!
-Gordon
Fairy wands and hypothesis slides; reflections on teaching MCB220L
By Dan Starr
The past three years I had the opportunity to teach the incoming BMCDB students in the rotation course. I was lucky to have great partners in this endeavor, Ted Powers for the first year, and Jodi Nunnari the past two years. The following are some of the highlights from my experience.
Far and away the best thing about teaching this course is the way I got to know the whole class, and watch them as they work hard to constantly improve their skills! I now know the students of these three classes better than any faculty member in BMCDB, and I can say with confidence, we have an awesome group of students!
We made some significant changes to the curriculum of MCB220L. I think the most important change was the requirement of writing an NSF-style grant proposal at the end of each rotation. This not only teaches the students how to write grants, but more importantly, gets them to think about the big picture before joining a lab. I feel this exercise was very successful. Especially to Amy, Nadia, and Alex, who turned their assignments into NSF fellowships—congrats you three! For all the other students, I think the assignment made you better scientists.
The second addition to the curriculum was the chalk talk. This is an important means of scientific communication that was completely new to the students. I hope that with the experience (and stress) of the chalk talks, now any of my students can give you a 5-10 minute version of their research at a chalkboard in a chance encounter in the hallway.
There were of course humorous moments to teaching the class—Ralph’s “pointer” comes immediately to mind. The other occurred at the MCB NIH training grant retreat at Fallen Leaf Lake when all the then second years cornered me after my talk. I still can’t believe I forgot the hypothesis slide!
In all, teaching MCB220L was one of the most rewarding things I have done as a professor! Watching my former students give a talk or hearing about them get a grant fills me with pride. We have an awesome group of students! I’m sure Bob, Elva, and Enoch will continue the high quality experiences of the class. Have fun!
In the boiler room of the Titanic
In today’s Science Dr. Henry Bourne and Dr. Mark Lively write an editorial arguing that the current state of biomedical research funding is like the Titanic heading for a collision with an iceberg.
http://www.sciencemag.org/content/337/6093/390.full
If the biomedical enterprise is the Titanic, then current graduate students are like workers in the boiler room. We have a repetitive job to do in a windowless room that smells funny and is full of toxins. Putting the metaphor aside, graduate students should pay special attention to the issues in the editorial- what is the state of future funding? who will provide funding? for what will funding agencies pay? I find it easy to focus on the immediate goals- what controls do I need to run? will this get published? will I ever graduate? However, the issues facing the field are important because graduate school should be training for the next step, and the best way to train is to know what that next step will look like. Some might point out- if we are in the boiler room of the Titanic our job is to make sure that the engines are powered enough that the ship can turn when needed to avoid the next iceberg.
Happy Independence Day (4th of July): Scientific Grilling Tips
As you get ready for a day of celebration and revelry, you will no doubt come across a grill sizzling with some tasty morsels. However, chances are that the guy standing there in flip flops holding a beer and poking at everything on grill doesn’t actually know what he is doing! The biggest mistake made in grilling is people messing with their meat too much, for steaks and burgers put them on and leave them alone until juice pool on the top and they are ready to flip. If you want nice criss cross grill marks on your steak just turn 90 degrees after 2-3 minutes, wait another 2-3 minutes and then flip and repeat (most steaks should take 4-5 minutes per side to achieve medium rare). When grilling chicken the best way to do it is by splitting your coals, have a hot area with most of the coals underneath, and a cooler area without lots of coals underneath. Start the chicken skin side down on the hot side, get a good sear all the way around and then move it over to the cooler side to finish cooking. Thighs and wings will take longer to cook than the breast so start them before putting the breast on the grill. Also extremely important to grilling any piece of meats is to let it rest for 5-10 minutes under tin-foil to let all the juices redistribute in the meat.
Happy Grilling from the BMCDB Bloggers
Here are some more tips and explanations of the science behind them.
Excerpts from
“Grill Science: How to Make This July 4th The Tastiest Ever” By Stephanie Pappas, LiveScience Senior Writer
What happens to meat as it cooks?
Meat goes through a few stages when you put it over heat. At about 110 degrees F (43 degrees C) internal temperature, muscles fibers begin to coagulate and toughen, Joachim said. At around 115 degrees F (46 C), fats start to melt.
When the internal temperature of the meat hits 130 F (54 C), the proteins in the muscle fibers denature, meaning that long, convoluted strands of protein lose their shape and unravel. Then they coagulate back together. That’s when meat starts to take on an opaque look. At 160 F (71 C), the connective tissues that hold together the muscle fibers start to melt and turn into gelatin. That’s the jelly-like yellowish-white stuff you see at the bottom of a roasting pan that you’ve cooked meat in, Joachim said. [7 Foods Your Heart Will Hate]
When you barbecue, Joachim said, the goal is to use those long, not-so-hot cooking times to melt the connective tissues and create barbecue’s trademark tender mouthful. Grilled cuts of meat usually contain less connective tissue, so they don’t need hours of heat to taste delicious.
Does it matter if I cook on gas, charcoal or a wood grill?
Absolutely, Joachim said.
“The big difference is the temperature and the moisture,” he said. “Charcoal and wood burn hotter and drier than gas.”
That’s because propane contains moisture, Joachim said. For every hour of grilling on gas, you release a half-cup to a cup of water vapor into your grill. That keeps the temperature down and prevents the formation of a seared, browned crust on your meat.
Some gas grills now come with a sear burner, Joachim said, which is a ceramic block that holds heat better than the grill grates. Because the burner can build up more heat, home grillers can use it to brown the outside of a steak or pork chop to get that dark crust.
Okay, but why does a seared crust taste so good?
Time for a chemistry lesson: When you apply heat to meat, you get something called a Maillard reaction. The amino acids that make up the meat’s proteins react with sugars in the meat, creating hundreds of flavor compounds.
Maillard reactions make pretty much everything taste awesome, including roasted coffee, grilled vegetables and even your morning toast.
“Any browned food tastes so good because it’s something new added to the food,” Joachim said. Browning doesn’t just lock in flavors; it creates new ones.
What’s the key to the perfect Fourth of July burger?
“The trick with ground meat is once you grind up meat, you’re grinding up the muscle fibers, and these are what hold the moisture in,” Joachim said. “What I recommend doing is adding moisture back in.”
That added moisture can take many different forms, Joachim said. He uses apple butter in turkey burgers and steak sauce in hamburgers. Simplest of all, he said, you can just mix ice water into the ground meat, along with whatever seasonings you want to use to spice up your burger. The ice water adds in moisture while keeping the inside of the burger cool so it doesn’t overcook. [Grilled to Perfection: Joachim's Recipe for Bison Cheeseburgers with Horseradish Mustard]
Fat is another important component of a good burger, Joachim said. He recommends a ground beef that’s 80 percent protein and 20 percent fat. Contrary to popular belief, though, extra fatdoesn’t make a burger juicier. Instead, fat stimulates saliva production, moistening your mouth.
When you add fat to a burger, Joachim said, it’s not getting juicier: “You’re getting juicier.”
We are one year old!
This blog has been up for a year now. Let’s review what this blog has brought you so far and this blog’s statistics are:
First of all, how many page views did we have?
A total of over 41,000 to date, with the best day hitting over 3,000. The first few months produced on average 40 hits for weekdays and a bit less during the weekend. A trend that has maintained to date. Following the first big hits of our blog, our hits improved from 40 to 80 hits a day. The graph below shows the two months that stand out. November 2011 brought us the pepper spray incident, which this blog covered extensively. The second month that stands out is February 2012, which was sadly marked by the untimely death of Christina Takanishi. Seasonal slumps are also very obvious, and because of that, we anticipate reduced traffic during the upcoming summer months.
Which blog entry was most frequently visited over time?
Of course, the home page is the most visited page, in part because people search for “BMCDB” frequently, and this blog pops up in the first 5 hits. Several of the other top hit pages are related to the two events are mentioned above, thus really belong to incidental top hits, rather than pages that continuously being visited. But there are two pages that are very frequently being visited to our surprise: Science: public perception vs reality and Panda’s are more diverse than Caucasian humans.
Where do most visitors come from?
Not surprisingly most visitors are native to this country (USA that is, with 7,000+ visits), but overall this blog has had visitors from all over the world (all 6 continents represented on the map). Whereas all the other stats cover the entire time the blog has been in existence, this particular stat has only been available since February 25th, 2012. If you know people in other countries that have not yet visited this blog, please direct them to our blog to complete this picture. 
How do people find our blog?
By enlarge people find our blog via google searches, which is not surprising as we are the second hit when searching for “BMCDB”. Many of our posts are also posted on the BMCDB Facebook page, directing traffic to our blog. Some of the big references came when several of our postings on the pepper spray incident made it to Reddit, fueling our page hits, especially on November 21, 2011. All our most recent posts are instantly tweeted via @BMCDB, directing people frequently to our blog, especially when other people retweet our postings (notable mentions to @phylogenomcs, @kbradnam, @kalpasjack1 and @DPMelters).
What search terms do people use that direct them to our blog?
Sadly the most used search term is “Christina Takanishi”, which is understandable as many people were touched by her untimely passing and wanted to share their feelings. On the other hands a notable search term is “uc davis student community center” or “student community center uc davis”, which directed them to this blog entry, which comes in as the 5th hit in a google search. “BMCDB” and “TGIF” are also frequently used search terms, which don’t need much explaining.
What does the future hold for this blog?
More contributions by different BMCDB students. If you would like to write a piece about something that interest you, or want to bring to people’s attention or just because, just send it to BMCDB.UCDavis@gmail.com. If you recently published an article as a BMCDB student, this blog is a great way to do some self-promotion, especially if you use plain language as well as tell the story behind your publication. Do you have a tasty science-infused recipe, don’t keep it to yourself, but share it with all of us.
Above all, please keep returning to this blog to stay updated with the latest development at UC Davis, the BMCDB graduate group or just for interesting or funny science tit-bits.
BMCDB Editorial: UC Davis’s Own LEED Platinum Sustainable Winery
By Gordon Walker
With much thanks to Dr. Roger Boulton of UCD V&E
UC Davis is an innovative and amazing University that excels in many areas. From our roots as a Land Grant Agricultural school to our myriad of nationally ranked departments, graduate groups, and professional schools; no facility stands out as much, or is as representative of the true Davis spirit than the Pilot Winery, Brewery and Food Processing facility at the Robert Mondavi Institute on the south side of campus. The building is the culmination and crowning jewel of the RMI, which was made possible by an incredibly generous donation from the late great Robert G. Mondavi. Since starting at Davis I have had the chance to watch the building go from a construction site, to a fully operational research facility that is not only revolutionizing the science of food, wine, and beer but also pushing the boundaries of sustainable architecture and agriculture. This building has been LEED Platinum certified, meaning that it meets and exceeds the requirements of the US Green Building Council to be a “green building”. What is so amazing is that this is not just a “green” building but also a functional research facility capable of super sustainable food and beverage production. This building can serve as a model not only for wineries of the future, but also as a starting point for any structure or complex.
The winery features 152 mobile modular fermenters with the capability to do real time wireless monitoring of sugar levels, allowing students to actually track and manage their fermentations through their smart phones. These 152 fermenters are also linked to a ventilation system that works to sequester and trap carbon dioxide as calcium carbonate, this system greatly reduces cooling costs in the winery and provides a value added product. The brewery features a state of the art Clean In Place (CIP) system that allows the entire brewing process to be done “in line” without any chance for contamination. The brewery also features a state of the art computerized brewery management system which allows students to mimmic commercial conditions but in small scale productions. The food processing facility is a large modular set of machines with capabilities to process a wide variety of crops such as tomatoes, peaches, almonds and other California staples. There is even a soon to be opened dairy processing facility that will serve to find practical solutions to problems faced by industry. While I could go on and on about all of the cool features of the Pilot facility, and the soon to be built Jess Jackson Sustainability Building, I will let Dr. Roger Boulton espouse some of the concepts and features that make this project so special.
Watch Dr. Boulton’s incredible power point presentation of the capabilities of the Winery and Jess Jackson Sustainability Building
Dr. Boulton’s Power Point Presentation
Long quote on the importance of the UC Winery Dr. Boulton
First LEED Platinum Winery, one of the highest (the highest?) point scores with 60 out of 69. One of 16 buildings at this level in 2011. It is energy and water positive as a building, probably the only LEED Platinum building to be so. It has gone beyond the LEED points for on-site water and energy, so a friend called it "Platinum plus" The 152 research fermentors make the largest research facility in the world and with its wireless density and temperature sensors, the largest wireless network in the fermentation world. These fermentors has several innovative design features, from carbon capture, water-only heating and cooling for temperature control, mobile and suitable for both red and white wine fermentations. The Jess Jackson Sustainable Winery Building is in the detailed design stage, and will be completed in Feb 2013. It is a passive utility building that will house the membrane systems for the filtration of all rainwater and cleaning solutions. It will house the carbon dioxide sequestration columns that will make calcium carbonate, the passive solar hot water, and the solar powered ice maker for the chilled water. It will make hydrogen electrolyticaly from solar power and store it for a hydrogen fuel cell for night time energy. These systems will be leadership commercial systems that will make the Winery self-sustainable in water and energy from on-site sources. This building will have insulations values between 60 to 80, compared to 20 in most houses. It will be among the most thermally-insulated (and therefore energy-efficient) buildings in the world, cooled only by night-time air. While the summer air temperatures might reach 100 to 105 in Davis, the building will not go above 82 F inside. The rainwater capture from the three buildings of the Robert Mondavi Institute will be held in 6 x 40K gal tanks, like the 4 that are at the south side of the Winery complex. It will be filtered into RO water over a 6 month period. This will require about 1 or 2 KW for 180 days but is a preferred alternative to a filtration that is completed in a week, at 26 times the KW requirement and sits idle for 51 weeks. The entire winery has been planned so that it can operate on storage rather than on-demand systems for all water and energy. The cleaning solutions will be simple inorganic buffers, dilute KOH and KHSO4, at pH around 11 and 2.5 respectively. No pathogens grow in either solution and hydrogen peroxide is a sterilant at both pHs. These solutions can be re-filtered through a nanofilter for 90% recovery of both water and salts. After 10 cycles this will require only 1/5th the usual water and chemistry. The solutions will be pH 7 when mixed and can be used in irrigation without any clay destruction, a problem with sodium salts. There will be no phosphate for algal blooms in streams, no nitrate for soil nitrification, no organic to contribute to BOD (biological oxygen demand) or COD (chemical oxygen demand) requiring waste water treatment. The 10% retentate stream which has most of the juice or wine organics will go to the biodigestor on campus to become biogas. All of these facilities have been privately-funded at a time of recession and financial problems at the State level and budget cuts at UC. It is a stunning example of what is possible without any government support and speaks to the wide array of personal support that we are fortunate to have.
Dr. Roger Boulton gives a tour and explanation of the UC Davis Winery
Here are some other press articles about the innovations of the UC Davis LEED Platinum Pilot Winery, Brewery and Food Processing Facility
Nanopore Sequencing – a New D(N)Awn, a New D(N)Ay?
In 2000, former President Bill Clinton held a press conference, to unveil the recently sequenced human genome. After 10 years of blood, sweat and pipet-tips, the project to sequence, assemble and annotate 3.2 Gb of DNA was finished. Well, not really finished, but a pretty good draft, as many iterations of the human genome have been published since that day. At a cost of $3B it was not cheap. The project was sold with many promises, most of which have not been materialized as advertised, but then again, when is an advertisement accurate?
Researchers didn’t just focus on analyzing every base pair of our genome. Some were working on developing sequencing techniques that were faster and cheaper than Sanger sequencing. These efforts soon gave rise to Solexa (later bought by Illumina), 454 (later bought by Roche, who are now trying to buy Illumina), and SOLiD (Applied Biosystems). Today, Illumina is the standard for de novo whole genome sequencing, whereas SOLiD sequencing has not spawned as hoped. In the days that the Human Genome Project started, people were theorizing of sequencing in a radically different way, without the use of enzymes or PCR steps, but using semiconductors and nanopores.
Although Oxford Nanopore Technology’s announcement at the AGBT 2012 meeting lit up the blogosphere last month, a year earlier Pacific Biosciences went public with the first single molecule real-time sequencing machine. The machine is a bit on the larger side (it needs it own room). You need a fair amount of starting material for the current protocol. And it takes a long day of preparations to go from your starting DNA to loading a PacBio cell into the sequencer. At the AGBT 2012 Oxford Nanopore Technologies introduced the first USB-sized sequencer, which doesn’t need any sample preparation. The promise of a $900 USB-sized sequencer blows away any not shown experimental results. The biggest limitation is that it can only sequence up to 900 Mb per sequencer, or just 0.33X coverage of a human genome. The USB-sized sequencer called MinION (see picture) and the larger DVD-player sized GridION are expected to hit the shelves in the second half of this year. Does this mean that there are no competitors on the market? There are. Quickly after the Oxford Nanopore Technology’s coming out, Genia came with a press release claiming that they will hit the market in 2013 and their technology will allow people to sequence their genome for less $100. Of course, a sequenced genome does not mean that you know what you have in your hands, as you still have to analyze it.
How does nanopore sequencing work? Using an array of mutant transmembrane proteins that from the nanopores which are embedded in a polymer membrane. Through this nanopore a DNA strand will be ratcheted. A sensor array chip consists of microwells and each microwell has it’s own electrode. Application-specific integrated circuits, or ASICs, apply a potential across each nanopore and measure the ionic current flow (see figure), and as each base pair creates a unique disturbance of the current flow. Following the current flow disturbances the sequence is determined. The sensor chip is contained in a cartridge that contains all the reagents needed for an experiment.
This does not mean that sequencing techniques such as Sanger or Illumina will go extinct. If you want to quickly check if your favorite plasmid is what you think it is, a simple Sanger sequencing run would do. If you want to know where a certain protein binds in the genome a simple ChIP-chip or ChIP-seq would do. Illumina, 454 and Sanger sequencing will be forced into their own niche, as microarrays has done after Illumina and 454 came on the market.
The future as depicted in the Sci-Fi movie Gattica looks to be at the horizon. Assuming that Oxford Nanopore Technologies and Genia will be as successful as they advertise to be, how will/can they change the world as we know it?
Whole Genome Sequencing
The biggest hurdle dealing with Illumina and 454 sequences is assembling the millions if not billions of short reads produced in useable contigs. The human genome consists of 23 contigs, better known as chromosomes, and each of us has two copies of each chromosomes (except for sex chromosomes in males). Most contigs that are produces from Illumina and 454, as well as from Sanger sequencing are in the order of Mbs and don’t cover an entire chromosome. To facilitate the assembly process of short reads, an assembly competition was created, called the Assemblathon. These competitions will be rendered useless if nanopore sequencing can produce single DNA reads that are larger than most contigs produced by assembling Sanger, Illumina or 454 data. A 98% accuracy would not be a major hurdle, as a 20-30x coverage is already required for assembly of Illumina data. Re-sequencing all (eukaryotic) species that have been sequenced to date might not be a bad idea to greatly increase the contigs sizes. Sequencing through regions of our genome that cannot be assembled, such as the centromere would be trivial. Finding duplicated or inverted regions at base pair resolution would be easy as well.
Allele Genetics / Population Genetics
The field of population genetics will change, as it would be possible to sequence each allele individually (you have 2 copies of each chromosome, one from your father and one from your mother) and trace their origin within a population. Also getting a recombination map at base pair resolution and accurate mutation rate would be straightforward. The nice feature of the USB sequencer of Oxford Nanopore is that you can sequence your samples at location, which would mean that there is no need to prepare samples for shipment anymore.
Personal Genomics
A lot has been spoken about personalized medicine and companies such as 23&me that push for this development. Imagine you could go to the doctor’s office and one hour after a biopsy your MD knows the specifics of your tumor compared to your healthy tissue. Nanopore sequencing would make this possible. Fetal genetic testing would also become more genome based, but this would mean invasive procedures would become more prevalent, as DNA from the fetus in the uterus would be required. Sequencing your babies genome at birth, would allow for a quick scan of potential genetic predispositions for certain clinical traits. Although a lot of ethical concerns have been brought up, little hard evidence exists that support the hypothesis that people with have problems dealing with personalized genetic information. It has to be kept in mind that everyone (or just about everyone) knows a fair bit about their genetic risk for certain diseases. If heart-disease runs in the family, there is an increased chance that you might get it as well. Selection based on genetic information happens already. Why would you be sexually attracted to one person and not to another? Overall, genetics already is a major part of our lives, whether we know the actual DNA sequence responsible for it or not. Nanopore sequencing would make it possible to have your own genome sequence.
Forensic Genetics
Forensic DNA testing will be dramatically different as well. If you can bring your sequencer with you on the road and put your sample directly on the chip without much processing and plug the sequencer in a USB hub on your laptop, it would be possible to have a more accurate DNA picture (not just a fingerprint) of a suspect within 15-30 minutes. Just imagine that at a murder scene a blood spec is found that might be from a suspect. Rather than having to collect the sample, transport it to a forensic lab, process it for forensic DNA testing and print out a report several days later, you can now get a genomic scan of your suspect at the scene within an hour. The advancement of population genetics is pivotal. Cataloging DNA markers (SNPs, duplications, etc.) will be critical, both for geographical correlations, as well as morphological trait correlation. Of course, reality is going to be much more complex, but the prospects are glowing hot. Depending on how much starting material you need to do a sequencing run, you can accurately discriminate between multiple donors in mixed biological samples. At this moment this is a hotly debated field in forensic genetics, as different labs use different statistical analysis and subsequently come to different conclusions. If it would be possible to sequence each cell individually, in other words, if the starting material just has to be a single cell containing a genome (human red blood cells would not be very useful), discriminating every donor would be trivial. If the biological sample is human blood, the investigator should even be able to discriminate the B cell genome from the T cell genome, based on unique recombination events of either the immunoglobulin genes (B cell specific) or T cell receptor genes (T cell specific). Of course, private investigators will see many uses for this new technology as well.
Insurance Genetics
Insurance companies could see great advantages for their profits if they can very easily obtain your genome and estimate the likelihood of you getting a certain disease. Forcing you to pay a much higher premium or denying you healthcare all together. Linking your genomic information to other insurance (reduced impulse control for drivers, for instance) could save them a lot of money (or more accurately, make them a lot more money). Having regulation that limit or even prohibit companies or any other third-party for asking a DNA sequencing test (including prohibiting buying such machines), as well putting a tight limit on how many DNA sequencing tests you can order per time period per address could be considered. Than again, I am not a legal expert by any measure. The consequences of easy personalized genome sequencing needs to be address at the legal level.
Security Genetics
Security by DNA sequence. If you want to work in a high security environment, demanding a genome test to be put in the system would create a highly personalized level of scrutiny. If your genome test at the gate doesn’t provide a match to the existing record, you are not given access. For large-scale security applications, this would be too slow, but if speed increases it could even be applied to for instant airport security. Only people banned from flying would be in the system, and if you don’t match you are free to continue your journey. This would be a problem, as it is imaginable that family members are affected as well, if by random change only one allele set is sequenced. Having this to work, you would need several allele markers on different chromosomes to have an accurate map. Experience with such systems is obviously essential. In short, the sequencing time can be tracked in real-time, you could continue sequencing for as long as needed until you have a match or not a match depending on what you are matching to (inclusion or exclusion).
Disease Control
Being able to sequence pathogens at the scene would allow for accurate identification and tracking. For this to become more efficient, it would greatly help to get rid of human DNA. By only focussing on the non-human DNA present in a sample, this should be possible. In other words, only record non-human DNA sequences. A good pan-human genome would be essential in this case. Of course, this feature can also be used in an academic environment, but its use for public health could be immense.
Relationship Genetics
Many more applications will most likely be thought and some of these applications will be far out there. One such an application could be: an internet company that offers coupling of individuals based on their genetic diversity. In other words, how to create the most genetically diverse child possible if a relationship works out. If this will happen is remains in the future, but it is certainly an option.
What do nanopore companies have to do to jump from the DNA era into the genome era?
- show you can sequence a genome anywhere, anytime, easily and reliably without much if any sample preparation
- how starting material is need (one cell would be ideal of course)
- how to sequence more from less (increase the sequencing capacity of the sequencers)
- an easy to use interface, both hardware-wise and software-wise (new programs have to be written)
- promote open access and open science to facilitate collaboration with and between scientists
- have the capacity to produce high quantity and high quality nanopore sequencers soon
- find a way to recycle large quantities of used nanosequencers
Editorial-The DEB is a unique graduate program to enhance your PhD experience
By Dr. Judy Kjelstrom, director of the UC Davis Biotechnology Program and Program Coordinator of the DEB graduate program (www.deb.ucdavis.edu)
I recently co-authored a journal article showcasing this innovative graduate program which was established in 1997. We currently have 225 PhD students from 29 graduate programs. The title of this manuscript was “A Collaborative Model for Biotechnology Education and Training”.
Recent reports and a careful analysis of the job market for doctoral graduates suggest that innovative approaches and training models are needed to realign educational practices with 21st century marketplace demands. The Designated Emphasis in Biotechnology (DEB) is a successful model for meeting current training challenges in life science and engineering doctoral programs, which includes formalized coursework, informal training in team-based science, entrepreneurship and effective science communication, and exposure to “real world” research environments via internship experiences. The DEB program is effective not only because of carefully designed curriculum and training activities, but because it is nested within a robust innovation ecosystem, including administrative centers and institutes focused on creating public-private partnerships and brokering new technologies. Within the environment of a technology hub, universities and private partners can bring together diverse groups of individuals to translate ideas into real world applications. This environment gives rise to a social networking mechanism that links the intellectual and human capital of the university with the financial and social capital of the regional marketplace.
Our success is being recognized at the State and National level. I was invited to speak at the Annual California Biomedical Innovation Night on Feb 9, 2012. The focus of my talk was how the DEB graduate program is a successful graduate program that links academia to industry and government.
http://californiahealthcareinstitute.blogspot.com/2012/02/speaker-spotlight-judith-kjelstrom-phd.html
As a result of this speaking opportunity, I was interviewed for an article for Science Careers. The focus of the article was how PhD programs can link students to the real world. This is a similar article to the one that was published by Nature Reviews in March 2008. http://www.nature.com/nrd/journal/v7/n3/full/nrd2542.html.
The DEB program was also featured in the 2010 California Biomedical Industry Report by CHI (California Healthcare Institute) as well as an article by Nicole Guimond Gravagna, PhD candidate in Neuroscience, University of Colorado, Denver. The title of the article was “Creating alternatives in science” in the Journal of Commercial Biotechnology (2009) 15, 161 – 170. doi: 10.1057/jcb.2008.51; published online 18 November 2008..
UC Davis and its partners are addressing the need for innovation and entrepreneurship in graduate education and training. By bringing diverse experts from the life sciences, engineering, humanities and business community together, we have built an innovation ecosystem capable of accelerating the translation of research discoveries into real world applications.
bmcdb
