Patent Bar Incoming? To be continued...

In a new take on future career developments, I am looking into taking the U.S. Patent Registration Exam (USPRE). At a low $150.00, the 3 hour computer based exam from United States Patent and Trademark Office (Prometrics website) gives you the right to act as a Patent Agent, to provide counsel and submit patents.

The exam is "open book" and based on the Manual of Patent Examining Procedure (MPEP).

If you are interested in checking out what it looks like, past exams can be found here and here is the practice exam book that I am planning on picking up to study for it.

I have only slightly toyed around with the idea of going into patent law before this, and I doubt that it will change my longterm career direction. I am pretty set on developing new uses for microorganisms and I expect that it will help me out along the way.

Too Many Graduate Students; Not Enough Jobs

Today, I offer two articles. The first article is from Scientific American about the current state of the US science and engineering job market, while the second deals with an alternative model to PhD education being explored in China.

Does the U.S. produce too many scientists?
This story by a really eye opening article on how the US overproduces scientific PhD's for the job market and how this bizarre system is maintained through the recruitment of foreign students to fill the ranks.

What I got out of the article is that:
1) US K-12 still produces some of the best graduates in the world. There are some big gaping holes in the public education system that merit fixing, but we should acknowledge that it still produces some really good students.
2) Those students who want to make money don't go into science.
3) Those that do go on to graduate school in science join a grant funding system which supports lots of cheap labor in the form of graduate students and "temporary" postdocs. Then when they graduate with PhD's and want to start their own labs, they discover that there are way too many PhD's for the number of career jobs available.
4) One solution is to switch funding from temporary postdoc's to longterm staff scientist positions. Another is to cap the number of foreign graduate students who are admitted to study in the US and make the cap respective of the market.

I don't feel like I know enough to comment on policy, but I am already weighing options for PhD work and I haven't even started grad school.


Do scientists really need a PhD?
BGI, a Chinese genomics institute doesn't think. The suggested model would be to jump into a research project right out of college without the typical PhD educational experience. While I may be a bit biased, my three years of lab tech work seem to be very similar to what PhD student would go through, minus the required classes and grades. While I look forward to being the first PhD in my family, I truly doubt that the letters, by themselves, will make me a better scientist. I believe that it is the hard work, scientific problem solving and long discussions with colleagues are what make the scientist.

Lonnie Ingram: Engineering E. Coli for Fuels and Chemicals @UT 2/24/2010

Two weeks ago, Lonnie Ingram came and gave a talk here and I had a chance to take some notes which I will share with all of you as well as some of my thoughts.

Introductions...
Most fuel in the US is produced domestically. However we still import lots of oil for fuel and coproducts (like solvents).

Biomass is used in three processes right now US Whiskey (from corn), Brazillian Rum (from sugar cane) and University of Florida's Tequilla process (from lignocellulose, hexose and pentose aka starchy stuff like switchgrass ).
Production from cellulose requires acid/base pretreatment which creates inhibitors to cellulases. Usually by dropping the starch in a tub of acid or blowing it up. Then you can mix it in with your bacteria or enzymes in the fermenter.

1. Engineering Organisms for increased yields: Zymononas mobilis
By mucking around with this organism they were able to reduce the net energy loss into CO2 making the fermentation process more efficient. Then they eliminated competing reactions and then used increasing biomass as a selection marker for better ethanol production in directed metabolic evolution.

2. Increasing ethanol tolerance, the more the bug can stand the better for production. I don't remember any publication work that he mentioned.

3. Since there are multiple sugars in starchy sources its important to get the most out of them and he talked about the sugar co-utilization of xylose and glucose, and how it can be improved with mutations to methylglyoxal synthase.

4. Deconstruction and inhibitors: by using cellulases they showed how to skip the expensive liquid solid separation and wash steps and just go pretreatment (see above)->fermentation-> purification (getting your liquor out of the gunk). Now they just need to have the bacteria operate at higher temperature and pressure to get the cost down. The three major compounds which are extracted from the starch and function as inhibitors were furfural from hemicellulose (which Quaker Oats produces from corn hulls for use as solvent or in resins), acetic acid and hydroxymethylfurfural.

The first thing they did was look for a furfurol reductase using mutant screening. They found that sulfur relieved some of the furfural inhibition. Eventually discovering CysIJ reductase and that furans inhibit growth by depleting the NADPH pool.

6. Fermentation for co-production:lactic acid is a co-product in fermentation. They worked with a company to produce it for use in poly-lactic acid (PLA) for the production of bioplastic. Pediococcos IdhL. There is a big need for the production of D and L lactic acid to blend for bioplastic production.

7. Succinate is a key building block (on the DOE top 10) and work done by Xueli Zhang looked at improving yields through flipping pathways around to produce succinate from CO2.

He lastly mentioned how to promote synergy in the way plants are setup taking the waste CO2 from the fermentation part of the plant and producing succinate in another, I would expect to see networks like these in the world future biorefineries.

First Gatorade and now cellulosic bioethanol. The University of Florida really knows how to do technology transfer! Its really great to see academics pushing new tech into the private sector. This makes me cautiously optimistic about the chances of taking some tech that I develop as a grad student or postdoc to the market through a startup. I don't have anything yet, but I definitely have some ideas up my sleeve. Mr. Ingram failed to mention his funding sources but the idea of industry working with academics sounds like a good alternative source of research funding from the NIH/NSF.

2010 A Year of Hard Decisions: How to pick the best choice for a graduate program.

Recruitment Weekends Rock!
This past month has been a bit of a whirlwind for me. From just finishing up my applications to getting invited to visit my top choices for school, its been very rewarding to say the least. I visited UT's Cell and Molecular Biology Program on Jan 28th and 29th. Working in the building where the recruitment events were located was a bonus, as I got to finish up an experiment I was working on during the downtime at the end of the day. The event started off with a mixer at a hotel downtown where the non-local recruits were staying. The next morning we listened to some talks, went to a gigantic poster session and had some interviews with Faculty. The evening was topped off by a formal dinner and "magic show" downtown at Esthers Follies.

They say that everything is bigger in Texas, and the CMB program has over 120+ faculty associated with the program and growing. This is some consolation because even after working, living and breathing research at UT for over seven years, I still met Professors that I have never seen or talked to before. It was a great victory lap feel for me because of my lack of success at getting in last year and my residual envy of the recruits who did.

The Rice Biochemistry and Cell Biology interview was just as great of an experience. First of all, they flew me in on Thursday Feb. 11th and out again on Feb 13th. I know I could have driven but we only have one car and it would have been troublesome. Upon arrival, not only did they put me up in a great hotel, but my suite-mate got snowed in leaving me alone in what had to be 800-1000 sq feet of posh hotel excellence. The next morning I found out that only five recruits made it that weekend. The other two got snowed in. This was a bit of a shocker for me as UT had at least fifty people in attendance. Granted that was for CMB, Biochemistry and Microbiology, but vast difference in scale reminded me of how exclusive the "Texas Ivy" remains. Rice has some truly gifted Faculty. I met with six for interviews and each one seemed like they would make wonderful advisers. To cap the wonderful day Prof. Jonathan Silberg took us out for some of the best Thai food I have eaten.

Those recruiting visits presented a glorious end to the application season.

Invitations to study
I have since received invitations from both programs. This is very exciting news as less than a year ago I was furtively coming up with alternative career paths in the event that I didn't get into graduate school this year. Now, I had the pick of the litter and the hardest part is figuring out which top-ranked research institution will provide the best location for both both of our careers.

How to decide?
1) For those with a "pseudo-two body problem", consultation is absolutely necessary. This doesn't mean convincing or arguing, but a frank and dispassionate discussion with all the information on the table. A conversation devoid of personal desires and only hoping to find the best solution together.
2) Prayer and Meditation help to put things in perspective. There are a few prayers from the Baha'i Writings that really capture what I want better than I ever could.
3) Just roll the dice. We can't see the future and just have to try to make the best choice with the information presented to us.

A Vision of my Career: Finding the Alchemist Stone for the 21st Century

My favorite alchemist Hennig Brand by Joseph Wright.

These are exciting times for me as I gear up for recruiting weekend Rice and meditate on UT's recruiting event. I am preparing for the upcoming interviews with some of my favorite Professors by reading their papers and figuring out who I am and what I want to do. Today I will share with the entire world (or just those that reads this blog) why I do science and what I hope to accomplish in my career as a researcher.

Once, I dreamed of molecular dynamic simulations and being able to engineering enzymes to order. As I survey the field of protein engineering, I feel that we are in a much better place as far as making enzymes to order than when I first started following it in 2004. Now I feel that the struggle is to take the next step and build pathways to order. Perhaps I am overestimating the power of directed evolution, but I am confident that its only going to get easier.

My current vision of the work that I want to develop over the course of my career is the use of microbes (bacteria and yeasts) as chemical factories. Now we can use molecular cloning tools to copy & paste whatever enzymatic pathways we want into them, requiring only sugar for their augmented metabolism. I can't help but draw a parallel with the famed Alchemist Stone, which was reputed to turn lead into gold. This "alchemist stone of the 21st Century" will be the methodology combining protein and metabolic engineering. Believe it.

In stepwise manner we turn lead (sugar or cheaper carbon sources) into precious gold (i.e. expensive pharmaceuticals and specialty chemicals):

1) We select a production chassis. This will probably be bacteria (E. coli) or yeast (S. cerevisiae).

2) We clone out the production pathway from libraries or other organisms into our chassis.
a) If no enzymes exist for that chemical reaction, protein engineering provides a toolkit such as directed evolution to evolve it from similar enzymes.
b) Computational simulation provides an alternative to directed evolution by making educated guesses about mutations which may produce that activity.

3) Next the pathway must be optimized in the microbe for maximum flux. Techniques for this involve modeling the pathway based on production in intermediates and up-regulating the steps acting as a bottleneck. This can be done one enzyme at a time or using directed evolution.

4) Now that the pathway is in the microbe and producing the most of our "gold" possible we can opt to switch its "lead" to something else which is cheaper (plant biomass, recycled plastic, or even urban refuse) in similar manner as putting the production pathway in.

5) Last we can include a production "switch", in the form of an inducible promoter, that we can turn on to push the microbes to the limit before we spin it all down and collect our hard earned prize.

These microbes can be freezed down, dried out and otherwise sent anywhere for production of your product. Thus technology transfer within a company or between countries is easily facilitated. The final purification may be tricky to get setup at a biochemical plant, but growing microbes is easy and straightforward.

Therapy lets paralyzed rats walk again; Old News is still Good News

Here is a really cool nature article from back in September, while I was on break from this blog.

Transformation of nonfunctional spinal circuits into functional states after the loss of brain input

And the synopsis from Science Daily.

These rats hat their spines cut to prevent any movement of signals from their brain. Then their walking movement was restored using a combination of electrode stimulation and drugs.

While we aren't quite there at repairing the damage to the spine, by recreating that movement your muscles can retain/rebuild their memory which will be helpful in physical therapy.

As a child, after learning all there was to know about dinosaurs, I moved on to dreaming about making prosthetic limbs. My plans of going into biomedical engineering ended when my parents gave me a book on Genetic Engineering, but I still love to hear about exciting developments for the physically impaired.

Organic versus GMO; An Alternative View

Organic foods are a hot issue.

I love feedback from my ideas. I welcome it. I adore it. On my own I know very little, through talking to other people I can learn a lot.

Today I will introduce some more details on my views on GM/Pesticides vs Local-Organic-Heirloom Crops. I will refer to them as "big-ag" and "little ag" practices owing to the David versus Goliath nature of the current paradigm even though I recognize that organic foods are big business and are not solely produced by small local co-ops. The following is a very brief description of what I see the differences between big ag and little ag models.

Big Ag Practices

• Pesticides and excessive fertilizers which lead to algal blooms
• Genetically Modified Seeds (bigger, faster, stonger but... see my previous entry)
• Whatever Monsanto sends in the mail
• Shipping across the world long before they are ripe
• Super cheap and available at the supermarket up the street
• Mostly lower nutritional content (picked off the vine green and ripens while shipping)

Little Ag Practices

• Creative Farming Techniques which reduce the need for pesticides and fertilizers
• Natural Genetic Variety (protection against pathogens, see potato famine)
• Heirloom seeds
• Shipping across the city or even being picked up from the farm
• Farmers market, Co-Op, or harvested in your own backyard
• Mostly higher nutritional content (picked off the vine ripe)

As the median real-income of the world grows we are going to see a burgeoning middle class which can afford higher quality of food. However, we can't feed all those people with little ag practices. We must blend the two models into something more... sustainable. Interestingly, its the people on the outsides of this middle class that are the major consumers of organic food because they are producing it within their community as they have for generations or because they can afford the better flavor and nutrition which local/organic produce provide.

Ironic isn't it?

There are plenty of people who opine about the terrible direction agriculture has taken and I think there is some value to that. For myself though, I am dubious about the added nutritional and health benefits of organic foods and have a problem paying a lot more for organic food at HEB. However, when I lived near the Wheatsville Co-Op, which sells organic food direct from local farms at a reasonable price, I went there as often as I could. This suggests to me that there is a sweet spot for little ag in our supermarket world we just need to explore different food delivery models.

Thanks for reading, I just wanted to point out that genetically modified foods and big ag aren't the answer to all our food problems.

Cutting US corn subsidies on the other hand...