Community

I am returning home from two exciting days at the National Science Foundations where I have been taking part of a funding proposal review panel. The review process is an integral part of how science is conducted in the United States and being asked to serve on a panel is considered a tremendous opportunity to give back to the scientific community. This was the first review panel that I have participated on and I was quite anxious about the whole experience.

I sat in the orientation meeting, towards the back, observing, taking in the experience. There room was about half full. As people kept coming in, I saw some of the older members recognize faces and walk over and shake hands or hugs. Introductions were made, names were exchanged, it was like a reunion of friends who had brought their own friends along to the gathering.

At that moment I had an epiphany of what the term scientific community means. It is not this cold, calculating set of individuals who sits and passes sentence on the veracity of a particular new finding or that drives the acceptance of a new hypothesis. It is just that, a community of individuals from all walks of life; breathing, walking, sharing, egotistical, humble …

This is where I feel at home. In the midst of this community; scientists.

Scientific Sleuthing

I’ve always had a soft spot for detective novels. I even fancy myself a detective. Not like the ones you read about in pulp fiction made famous by Daly, Hamlet, and Spillane (to name a few), but a sleuth no less. I have spent the last couple of weeks playing detective in lab, you see. I am out on a hunt for molecules produced by these microbes I am studying. This type of investigative work is what attracted me to chemistry and biochemistry. At hand I have a set of known microbial metabolic pathways, a pretty good idea of what some of the intermediate and products are, a lot of chemistry knowledge, and a whole slew of really cool high tech tools.

The method is pretty straightforward. I feed my favorite microbe a known carbon source; it helps if I can radio-label a carbon or another atom on the substrate. I wait for a defined period of time, collect the media, and start the analysis. Step one: spin down cells, take off the supernatant, extract with dichloromethane, …

Yes, it is quite tedious, but many steps later, I have a small sample with metabolites extracted from the experimental microbial growth sample. Now the fun begins. First, what technique do I start with? The simplest is ultraviolet/visible (UV/vis) light spectra. What does the absorption spectra of your samples look like? Can you see something that resembles a conjugated backbone? How about an aromatic ring? Hints of structure here and there.  But then you ask, does the sample contain one or many kinds of molecules? Can I somehow separate these molecules?

In this next step I might choose liquid chromatography (LC) or gas chromatography (GC). Which technique I use depends on certain properties of the molecules I am looking for, are they water-soluble? Are they volatile? For water-soluble molecules I select LC and for volatile molecules I select GC. Both of these separation techniques have a mass spectrometry instrument (MS) attached, allowing me to get a sense of the molecular mass of each separated compound. I inject and watch the molecules fly. Every peak I see reveals a wealth of information about the compounds ‘vitals’. What is the mass of the molecule? Does it fractionate into smaller defined compounds with a known mass? Do the fractionation patters I see match a compound previously characterized?

Next, I isolate and purify the compound using LC, collecting the fractions that have my compound of interest and use Nuclear Magnetic Resonance (NMR) spectroscopy to try to resolve ambiguities due to configuration around enantiomeric carbon atoms. I use proton NMR and carbon NMR and study the chemical shifts I see in my purified sample. From these set of data, I can deduce whether I have a ‘R’ or ‘S’ configuration around my enantiomeric carbon and a host of other structural relationships.

In the end, I have a larges set of ‘clues’ from which I will build a chemical structure of the compounds isolated from the microbial growth media. But that is not enough. In order to stake a claim to a new molecule and possibly a whole new molecular pathway, I have to present my findings to other chemists and microbiologists, convincing them that I have done my sleuthing well. It is very tedious work and most of the time you do not find a new molecule, but every once in a while, you isolate something, a molecule never seen before. The thrill of finding what has not been observed before, drives me to explore the secret metabolic pathways hidden in these microbial species.

Stay tuned to see how this tale turns out. HHH

Is meat made any other way still as sweet?

I have spent the last couple of months reading journal articles on food processing and technology. Recently, a review article caught my eye – Meet the new meat: tissue engineered skeletal muscle (Trends in Food Science & Technology Volume 21, Issue 2, February 2010, Pages 59-66). Having friends in tissue engineering laboratories that tackle this challenging field of research, I was curious to read what the authors had to say regarding tissue engineering for food stock.

The authors state the case promoting research to develope engineered meats, arguing that the current trends in energy use, land use, and environmental concerns with greenhouse gas emissions dictate the development of alternative meat sources. They list some of the current uses of tissue engineering (such as medical replacement tissue and/or skeletal structure to help mitigate damage caused by disease or accident or for the in vitro study of key metabolic processes) and rely on these experimental results to discuss how they could lead to the generation of artificially produced meat products.

There have been exciting advances in the design and engineering of artificial matrices, which support cell growth, holding promise for the future of medicine and biomedical engineering, although there are many challenges still left to address. (Perspectives and challenges in tissue engineering and regenerative medicine, Advanced Materials, 21:  3235-3236, 2009; a good review of current challenges and strategies is covered in the February 10 issue of The Proceeding of the National Academy of Sciences). The ability to direct a drug of choice to the area in which it is needed, or to construct a bio-degradable scaffold for the introduction of regenerative tissue to a site of injury will alleviate many diseases which affect our quality of life. But, one thing all these therapies have in common is that they are designed to provide an affected body with the building blocks that will allow it to heal and restore itself.

Engineering and growing muscle tissue without an underlying or enveloping system to provide molecular instructions and guide cellular and structural growth changes the rules of the game. As the authors pointed out in this review, there are many factors that affect the development of the structure and function of muscle tissue. As of now, we do not have a complete understanding about the underlying cellular signaling and molecular decision-making pathways to ensure that the process of engineering and designing artificial meat will provide a sustainable and desirable product for human consumption.

The next barrier facing this research will be to scale up the process. What works at the bench or in a laboratory will not necessarily work in large-scale processes. Although much work has been done scaling up the production of medically relevant products using large fermenters, new plant and equipment design will be needed to address the challenges of tissue manufacturing.

If these challenges were to be met, and palatable genetically engineered meat products were produced, bringing these products to the market would generate another set of obstacles. Resistance to and fear of genetically engineered or modified foods by many people will have to be addressed. Governments and scientists need to educate their constituents and communities about the benefits, risks, and ethical implications of genetic engineered foods. Local and national regulation need to be enacted to provide commerce with direction and oversight.

As excited as I am about the possibility of eating an engineered ‘steak’ or ‘pork chop’, I believe that much work needs to be done before we see the commercialization of genetically engineered meats available for consumption.

An Anniversary to Remember

The Queen of Hearts
The Queen of Hearts

Three years ago at this moment I was sitting in a room in a hospital waiting.  Restlessly waiting, for the heart surgeon to stop by.  It was a beautiful cold and sunny day, just like today.  Christi was there.  She had flown in from New York City for a couple of days.  Mr. and Mrs. Burns were there. Mrs. Burns quietly reading, Mr. Burns checking his Blackberry, making sure every one was taken care of.  We were a bundle of nerves.

Lily had gone into surgery earlier that morning.  Open-heart surgery.  Not your normal lets change a valve or two surface scratching in your chest cavity brand of surgery you hear are so routinely done these days.  The doctor was going to stop her heart, cut into her heart, sow up a tiny little hole in the middle of her heart, and then close it all up in hopes to alleviate the cause of her recent stroke.

A little past 11 that morning, the doctor came in. He spoke with us and told us that the surgery had been a success. Just a short 8-10 minute operation. A routine task, for him, as he had developed this procedure. Lily would be in the ICU soon and we would be able to see her soon.

At half past noon, we were allowed to go see Lily. I still remember her laying there in the bed, with all those tubes in her. Later, as she awoke from the anesthesia, still groggy from the surgery and the pain drugs, she turned and smiled at me. I felt relief. The beginning of the road to recovery and physical healing for Lily and for us. The stroke that happened earlier that summer had been a life-changing incident. The open-heart surgery repaired that little hole, the culprit, of that devastating event. It did not stop us. We were moving on.

The last three years have been some of the best of my life. We still live with the aftermath of a stroke and open-heart surgery. This is now a part of our story. I am still amazed at her strength of will and at her courage. We were both lucky.  Living in Boston. Close to such great medical centers. An incredible support group of friends and family. But most of all, I am lucky for still having Lily in my life.  Thanks for all that you are and all you mean to me.  Besos.

If you want to know more about stroke and heart disease, please visit the American Heart Association web site. Please help stop the number 1 killer of moms, daughters, sisters, friends, and lovers in this country. Know the signs.

Padma Lakshmi opens the MIT Center for Gynepathology Research

The room was packed. We had received an invitation to sit in the special seating section and to attend the ‘after party’. Lily and I waited, in the third row, front and center.  Padma Lakshmi would be walking though those doors, stage left, momentarily. We’ve watched her on Bravo’s Top Chef for 6 seasons now.  Always so beautifully dressed, with her smile, knowing that she was ready to challenge the next set of top chef’s almost beyond their culinary limits. And for all but one, past that breaking point where they hit that wall and fell short of their gastronomic dreams.

Padma Lakshmi was at MIT for the official launch of the MIT Center for Gynepathology Research. This research center, the child of Professor Linda Griffith, is the first interdisciplinary academic research institute which brings together biologists, clinicians, and engineers with the goal of understanding the basic biology, physiology, and pathophysiology of the female reproductive tract.

Professor Linda Griffith began the afternoon by introducing Susan E. Whitehead, Lifetime Member of the MIT Corporation and Vice Chairman of the Whitehead Institute for Biomedical Research. Ms. Whitehead remarked on the bold research initiative embodied in the center. Dr. Tamer Seckin, President and Founder of the Endometriosis Foundation of America (EFA), followed her and introduced Padma Lakshmi.

There she was, tall, beautiful, poised, radiant, and very much pregnant. Ms. Lakshmi began to share the account of her personal struggle and eventual diagnosis with endometriosis. This disease slowly wrestled control of her life and body away from her.  She recalled of how she suffered alone with this recurring, debilitating disease, learning to tolerate excruciating pain.  Scheduling her life around the monthly assaults by this unbearable condition. Living every day with this incapacitating disease, one which until recently had no name or meaning to her. Her pain was apparent in her heart felt rendering of how she had suffered through misdiagnosis and unnecessary medical procedures before a friend referred her to Dr. Seckin. Padma told of the relief she felt hearing Dr. Seckin’s words.  He understood what she was going through.  His life’s work has been dedicated to understanding the molecular underpinnings of this debilitating disease.  Now, almost three years later, Padma tells of how she has regained control of her life and her body.

Through out her talk, Padma emphasized how the lack of awareness and education regarding endometriosis had shaped the medical diagnosis, treatment and response to her disease. She spoke of how social taboos deterred her from asking the right questions and demanding answers regarding her body and her physical state. She also described how the people who were closest in her life at times misunderstood or played down her symptoms, leaving her doubting her ability to properly describe her symptoms to others. It was not until Padma met Dr. Seckin that she finally understood the impact that endometriosis had had on her life.

What can you do as a woman, a partner, a loved one, for someone who is suffering with endometriosis? Education and information are the best tools to help you understand and identify the symptoms of this disease. Awareness of your body is key.  For those of us who care for our close ones, understanding and believing that when they complain, the pain and the discomfort they feel is real.  Do not brush it aside.  For all of us, do not hesitate to obtain a second opinion on a diagnosis.

In her closing remarks, Padma extended her heart felt thanks to Professor Griffith and the other members of the research center for making the MIT Center for Gynepathology Research a reality. For more information regarding endometriosis or other chronic non-cancerous diseases of the female reproductive tract please visit the MIT Center for Gynepathology Research or The Endometriosis Foundation of America.  Also, please read the article that appeared in the Boston Globe on Friday, December 4th.

Love at First Bite

I had known of her for a while. We crossed each others path. It was a rocky start. I asked her out. She turned me down. Twice. We saw each other at the coffee stand later that summer.  I was teaching biochemistry for high school students.  She invited me to stop by her office. I stopped by, later, my cart full of molecular models and biochemistry stuff. We talked.  She, sitting down at her desk.  Me, leaning against the filing cabinets by the window. Trying to be cool. As if. She asked me my age, 30? No older, 33? No older. Older than 35? Yes. So, she said, do you want to go have a drink sometime? Sure I said. How about this Wednesday?

I make sure I wear my signature straw fedora, a nice dress shirt, and one of my sport coats that evening. I dressed to impress. Too cool for school.

We went to a bar downtown. Made fun of people. Had some appetizers. Had some drinks. Talked food. Made more fun of people. Talked a lot about food. This girl got my attention. I dug her. She is leaving the following week on vacation. She and two girlfriends. Two weeks on a hot rock. In the middle of the Mediterranean. She promises me dinner when she came back. We walk to her place. One of those perfect summer nights in the city. Almost there, we stop for a quick nightcap. We talked some more. Drinks, a mojito, dirty dirty martinis, proseco. The summer night moves so quickly. I walked her the rest of the way home. She left me by the sidewalk, quickly closing the gate and dashing inside. Over the bridge I went. Back to lab. Intrigued by the evening. By her. I send her an e-mail in Spanish – the geek romantic that I am.

I don’t hear from her till Friday. How about that dinner before I leave, she said. Does Tuesday sound good? Yes, I said. Tuesday is good. What should I bring? Nothing, she said.

Tuesday comes. I am nervous. What is her food going to taste like? What about the flavors?  I am latino.  Cebolla, ajo, comino.  I need flavor, some adobo.  Does she remember discussing likes? Dislikes? We walk over the bridge, stop at the market for some limes. Walking on, casual but nervous chatter. We get there. I give her the bottle of dessert wine I brought. She pulls out a bottle of Havana Club given to a family friend by Castro himself and makes me a mojito. It tasted good.  Damn good. She knows how to make a mean mojito.

She starts dinner. Another mojito.  I feel warm inside.  The aroma wafting from the kitchen starts me drooling. Pavlov’s dog I am. She won’t let me nibble. She sets the table. The plating gorgeous. Colors blending with the scent invading my olfactory ducts. A frontal assault to the senses. I fight impulses, controlling the desire to devour. I take a first bite. Flavors burst in my mouth. Chicken, moist, falling apart under the tug of my fork and knife. Just the right amount of salt. The herbs convey a cool summer evening feel. Pears caramelized to perfection. The arugula crisp and fresh. A nice red helping to wash it all down. Then the coup d`etat. Home made truffles. 70% dark chocolate. Smooth ganash filling the crunchy outer shell.

Dinner over, we talk late into the evening. Another bottle of red, and another. Strong coffee. Steamed milk. She cast a spell over me. Enchanting me with her insightful observations, her long curly hair, her sensual body, but most of all her, snaring me in her gastronomic web.

It was love at first bite.

Thankful for being able to do what it is that I do …

This is what four days in lab looks like.
This is what four days in lab looks like.

It is 7:24 on the day before Thanksgiving. AC/DC is cranked up so loud my ears are starting to bleed and I have at least four more hours to go before I go home tonight.  There are papers and three lab notebooks strewn all over my bench top.  This is my fourth 18-hour day in a row.  A crazy look in my eyes and a five-day growth on my face.  A marathon set of experiments trying to decipher the growth curve of the community of deep earth microbes that I am trying to identify and characterize.

I started this morning over thirteen hours ago by coming in, turning on the gas to exchange the atmosphere in the anaerobic tent loading chamber, and promptly blowing out the seals in the CO2 regulator.  You know that when this happens at 6:30 in the morning, it is not going to be a good day.  I couldn’t find another one in the building (nor in friends labs in a couple of other buildings) so I settled in and waited until AirGas opened later that morning.  Needless to say, it was closer to 1:00 in the afternoon before I got the tent back operational, putting me at least five hours behind schedule for an already jam packed day.  So this is how I find myself with one more hour to wait while my microbial cells sit in the first incubation of many in a long protocol with which I will fix them in paraformaldehyde for later DAPI stain and FISH analysis.

Why do I do this? Why do I put in the long hours crazy hours?  Because I love it.  Plain and simple, that is the only answer I can give.   I delve into the unseen, the unreal, the unknown world of extreme microbes, and try to make it visible, real, solving the mystery of who lives where and how the hell they do what they do in those most inhospitable places in which they thrive.  I have to design an experiment with the full understanding that the equipment does not exist for me to do these experiments.  I cannot go to a shelf and just pick up one of these and three of those and have some technician come over and set it all up for me.  This is truly science driven by your capacity to design, invent, and assemble the equipment that you will need, while doing the experiments at the same time.

Sometimes I forget how incredibly crazy and out of this world what I do is.  I get reminded of this when I try to explain what it is that I do to friends and family.  I get this look of fear and awe when I explain that the things I study grow at 100-200 atmospheres, at temperatures between 50-75 degreed centigrade, and under acidic conditions so extreme it would peel the skin off your bones.  Like I said, this is pretty cool stuff.

Well, I got to go now, the next cell wash and incubation is about to begin.  While all this is extremely exciting, getting to that final answer is laborious, painstaking, and tedious.  Still, I would not trade this life for any other one.  This is what I am thankful for on this week.  I get to do what I love (and sometimes get a little frustrated at) every day.  Take care and have a great Thanksgiving.

Center for Alternative Technology – Paul Allen

Last Friday, Paul Allen from the Centre for Alternative Technology (CAT) in Machynlleth Mid-Wales spoke about the centers work during seminar in the Parson’s Lab.  He is the CAT Development Director and co-author of the Zero Carbon Britain (ZCB) report. Mr. Allen has spent the last month traveling the US from the East Coast to the West Coast by train giving his presentation about the CAT and the ZCB initiative.

The CAT advocates for an environmental policy that integrates current and emerging environmental management practices, new technology, and education to promote sustainable living communities.  Recently they partnered with University of East London to offer graduate programs in Architecture specializing in Environmental and Energy Studies, Renewable energy in the Built Environment, and Ecological Building Practices.  Mr. Allen’s work with CAT and the ZCB report is providing a policy and lifestyle framework which if adopted, can lower their dependency on fossil fuels and imported energy taking Britain a long way on the road to zero carbon emissions and energy independence.  Along the way, I hope they can provide a successful, sustainable environmental management model that can be used by other developed nations.  If you are interested in finding out more about the CAT, make sure to visit them online.

Thermoplasma acidophilum -a model organism to study iron stress in microbes?

Thermoplasma acidophilum. Linda Stannard, UCT/Photo Science Library.Microbes require iron (Fe) as an essential element for growth and development.  It has two environmentally stable oxidation states (II and III) readily participating in redox reactions covering a wide magnitude of biological electron transport and redox reactions including respiration, oxygen activation and binding, degradation of peroxides and superoxides, synthesis of DNA, proteins, and other organic molecules, and energy fixation pathways.  At the same time, unregulated iron uptake can lead to toxicity, reactive oxygen species (ROS) and to inhibition of growth.

Microbes have evolved an iron storage mechanism used to store iron under limiting or environmental stress.  The most studied system is that in Escherichia coli which produces three structurally and chemically related storage proteins; ferritins, bacterioferritins, and Dps (DNA-binding proteins during stationary phase).  Ferritin and bacterioferritin are a tetracosameric structures capable of storing 2,500 and 1,800 iron atoms respectively. Bacterioferritin differs from ferritins in that they have an iron protoporphyrin IX (heme) at the interphase of each subunit.  Dps is a dodecameric ferritin, which is induced under stationary phase of growth or by oxidative stress.  These supramolecular structures help sequester iron in the cytoplasm and prevent toxicity of free iron in the cytoplasm.

Microbes living in low pH environments are subject to high concentrations of metals, in particular iron.  How these microbes respond to metal stress is key to understanding how organisms control energy producing metabolic reactions in the cell.  Recently, the genome of T. acidophilum was completed affording us a glimpse of the possible biochemical pathways responsible for the survival of this organism in an acidic environment, but analysis of the T. acidophilum genome did not reveal any molecular pathways for the production of known iron storage proteins ferritin, bacterioferritin, or Dps.

How does T. acidophilum manage the high concentrations of soluble iron, or other metals, liberated by its acidic environment?  Does this organism have a novel iron storage mechanism?   What are the cellular responses to stress to T. acidophilum cause by high metal concentration in the cytoplasm or by ROS?  This is one of the questions that I am trying to answer using transcriptomics to look at differential gene expression of this Archeaon under varying iron and other  environmental stress conditions.

Of Chefs and Scientists

Last night I was watching Iron Chef America and there was a young aspiring chef pitting her culinary skills against Iron Chef Bobby Flay. I am always amazed at how the Iron Chefs prepare and pair their ingredients for the five courses. I started to ask myself, where do the ideas come from? How do they choose the color and the flavor for each dish? How do you choose the method for preparation and presentation?

When I woke up this morning, these thoughts insisted in occupying my mind. Lily and I spend some time discussing the kind of training and dedication that it took to gain a mastery of the skills necessary to achieve the title of chef. There is only so much that you can learn in a classroom.  The lessons learned in the o are then performed and perfected through practice and patience.  I remember my short time as a line cook and of the skill that was needed to keep track of the orders, to assure that the food was well cooked, and to make sure that a whole ticket came up at the same time, no matter how many things were on the ticket. I was really good on the line, but I did not come close to having the skill set or knowing the techniques that separate the good from the great.  I learned very valuable skills for food preparation and  presentation, but I never had the chance to apprentice, to follow a master and learn the secrets of great food design.

I have been extremely fortunate to have had a very different experience with my scientific training.  I have received some of the best academic training one could ho.  The interactions I experienced with my fellow graduate students and with the professors at MIT have honed my analytical and observational skills.  Working in the laboratory and developing the methods that allowed me to look at scientific questions using the best and latest tools gave me the confidence and the courage to branch out and try new research topics and fields.  Life as a postdoctoral associate is furthering my set of tools and tricks.

The real test of a chef’s skills are not on the line, but in how they can assemble ideas, ingredients, and skill in their head to give us dishes that inspire and complement our love for life.  Just like a chef, a true test of a scientist’s skills are not at the bench, but in how they can harness a hypothesis and through their skill, design well throughout experiments that increase our understanding and awe of the world around us.