When asked about the origins of synthetic biology, the most primitive, and first commercially expoited, example that comes to my mind is the construction of oligonucleotides for PCR. Oligo means short or small, and short-chains of nucleotides (DNA or RNA fragments) have become important tools in biotechnology and genetic research, ever since our ability to sequence DNA. In PCR, small pieces of DNA, usually about 15-20 base pairs long, are needed as primers. Oligonucleotides are also used for gene probing, a process for detecting certain specific sequences, and for enzyme optimization techniques like DNA shuffling and site-directed mutagenesis. We now have the ability to make much longer oligonucleotides, and technology is improving to make the process faster. According to a summary paper prepared by BIO for the 2008 World Congress, one of the most significant synthetic biotechnology breakthroughs this decade has been the in vitro construction of an entire chromosome, called PhiX174, in just 14 days. This achievement was reported in the journal PNAS by the J. Craig Venter Institute (JCVI) and team of scientists lead by Drs. Smith, Hutchinson and Venter, in 2003.

Travelling during a global pandemic is a risky business! I just got back from a trip to another province of Canada, a four hour flight away. While Ontario is handing out Swine Flu vaccine to the "priority groups" - small children, seniors and health-care workers, BC is facing a shortage and Alberta is dealing with bioethics issues arising from the public outcry over vaccination of the Calgary Flames, and a debate over whether firefighters are a high-risk group. One of the participants of a meeting I attended refused to shake anyone's hand for fear of getting sick, and last week I heard from a friend that children in her neighborhood of Toronto were not allowed to go Trick-or-Treating, because of influenza fears.

During my flight home I wasn't feeling the greatest and my colleague said, a little too loud, "I hope you aren't getting sick". I quickly told her not to say that too loud and looked around for the lynch mob that might throw me off the airplane at 10,000 feet. Every year there is a percentage of people getting the flu who die from it. In the USA, approximately 36,000 people die every year from the flu, although many of those are cases complicated by additional infections such as Pneumonia and Staphylococcus. This year, the US Centers for Disease Control and Prevention (CDC) has developed a new PCR-based diagnostic kit for detection of H1N1, which will not only help diagnosis but will aid in collection of more accurate statistics. In many past cases, flu patients also had known risk factors that compromised their immune system, but many don't, including roughly half of the pediatric cases. The CDC estimates mortalities due to H1N1 at somewhere over 1000, 114 of which were children, as of the end of October. Initial reports were that this strain had actually turned out to be fairly mild, so while people weigh the risks of taking the new vaccine against risks of getting, or even dying from H1N1, confusion abounds and we are experiencing the same sort of panic that prevailed in Toronto during the SARs epidemic.

Geron Corporation is a company based in Menlo Park, CA and the first biotech company in the USA to be granted permission for a clinical trial of regenerative medicine using embryonic stem cells, in humans. While permission was granted in January 2009, the trials were put on hold until last Friday (October 30, 2009) when the latest round of preclinical trials using animals revealed some side effects that warranted further investigation.

According to the Geron News Release, test animals receiving the treatment, GRNOPC1, developed a higher number of cysts at the area of spinal cord injury than in previous studies. However, the FDA has agreed to allow the studies to continue, since the cysts appear to be non-proliferative, confined to the injury site, and not associated with any serious adverse effects or SUSARS.

GRNOPC1 consists of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs). Oligodendrocytes are cells of the nervous system that produce the myelin shealth, which insultates the axons of nerve cells. Injection with the cells was shown to enhance remyelination of the spinal cord in adult rats. Demyelination after spinal cord injury contributes to loss of neural function. Rats treated with GRNOPC1 seven days after injury exhibited substantially better recovery and improved locomotor ability.

Geron expects re-initiation of the clinical trial in late 2010. Since the treatment must be applied shortly after injury, anyone wanting to participate in a clinical trial must agree to injections within 7 to 14 days of spinal injury.

Geron's pipeline also includes an anti-cancer drug and vaccine that target the telomerase enzyme.

_{Source: Keirstead, H. et al. 2005. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J. Neuroscience 25:4694-4705. doi:10.1523/jneurosci.0311-05.2005.}

Among those who work in biotechnology, there are three main areas of study: Biomedical, industrial, and environmental biotechnology. In just 15 years since PCR and gene cloning became a part of mainstream biotech research, industrial applications for the products of enzyme technology and GMOs have become competitive alternatives to traditional manufacturing processes, but still, few people are aware of how many everyday enzyme products have made it into their homes.

Biofuels still seem to have a long way to go before widespread use and acceptance validate the claims of their proponents. While the biofuels industry has it's critics, the arguments in favour include the use of renewable feedstocks. Many pharmaceuticals today are actually semi-synthetic molecules, made in fermentation processes by living organisms and later chemically modified, if need be. The costs associated with batch production, and complications pertaining to large-scale protein purification and equipment sterilization, are among the downsides to bioprocessing. The most well-known biotech product in the home might be enzyme-based detergents, like those produced by the widely recognized Novozymes.

Just about everyone is familiar with the story of stone-washed jeans and how they came to be enzymatically-altered. But jeans don't make an industry and biotech has yet to gain acceptance in many areas where the public is wary of the bioethical ramifications and potential health risks (xenotransplantation, stem cell research, nanotechnology). With so many complex issues to solve, will we ever become a fully sustainable, bio-based world?

Synthetic biology has been defined as the creation of artificial life forms, but, in reality, is more often exemplified in the creation of synthetic (man-made) building blocks of lifeforms, such as ribosomes, tissues and proteins and their ligands, that can be added together to create, or enhance, a biological system (as are studied in systems biology).

At University of California, Berkeley, Dr. Bertozzi and her research group study cell surface interactions and use synthetic biology to manipulate cellular processes. In doing so, they have been able to adjust the intercellular environment, control how the cells stick to one another, which affects their assembly into tissues. They reported using different types of genetically engineered cells to make artificial tissues capable of many of the functions of cell clusters, such as secreting and responding to hormones.

This work is really founded on the alteration of already existing cells, not the creation of completely new ones from scratch. The novelty of the work, however, is that tissues formed from these cells are like none other and can perform as no individual cell can. In systems such as this, the community of cells acts as a whole towards an end product of the scientist's design, such as large scale drug production. Smart polymers are also examples of synthetic biology, in that they are artificial polymer-based substances that can be designed to react in a cascade-like fashion to changes in their environment, much like the inner workings of a cell.

_{Source: Gartner, Z. and Bertozzi, C. 2009. Programmed assembly of 3-dimensional microtissues with defined cellular connectivity. PNAS 106(12):4606-4610.}

Systems biology is the study of how individual molecular components in a cell interact with each other to create active biological systems. This "grand scale" study of things generates information on the relationships between the structure and function of macromolecules (such as proteins), reaction dynamics (specific activity), and mechanisms for controlling reaction rates. These days, much of the information is built into models so that when new proteins with similar sequences are encountered, their systemic roles can be predicted.

The information obtained about the immune system, or viral and bacterial systems, can be used to produce better vaccines. For example, scientists at the Institute for Systems Biology are using what they have learned about the systems of the influenza virus to determine what makes one strain more potent than another. Some of this has to do with polymorphisms of proteins on the viral outer envelope, and their tolerance for remaining functional upon mutation.

For a complete lecture on this topic, the Institute has provided a 4-part video online.

Canadians can begin getting their H1N1 flu vaccines next week, now that the Health Minister has announced the vaccine is approved. There haven't been a lot of clinical trial participants in Canada, but the approval is based on European data. China began widespread vaccinations in late September, and the United States and Australia also already have programs in place.

The World Health Organization (WHO) announced on October 12 (2009) that about 100 low and middle-income countries will recieve donated vaccine starting sometime in November. The donations will be made by vaccine producers such as GlaxoSmithKline and Sanofi. The protection of health care providers in the recipient countries will be given top priority.

According to a poll taken in early October, only about a third of people intend to get a shot compared to nearly 45% in August. Might that have something to do with that flurry of attention given to an unpublished report (last month) that the flu shot for H1N1 could make you more susceptible to the regular flu? We are still waiting for the details on that one, but the blame could also be attributed to lack of confidence in the flu shot in general, or fear of adverse reactions (SUSARs).

Scientists at the University of Illinois are applying nanotechnology and stem cell research to study the impact of mechanical forces on stem cell differentiation. The group, lead by Dr. Ning Wang, used cells, to which a 4 micron diameter magnetic bead had been attached, to compare the softness of embryonic stem cells to their differentiated counterparts. A tiny oscillating magnetic field was applied to the cells and the amount of movement of the bead was measured and used to determine how firm the surface of the cells were. Dr. Wang determined that the movements were comparable to natural forces within a living cell, and postulated that cyclic forces might impact gene expression and cell development. The researchers used GFP to study the expression of certain genes in mouse embryonic stem cells and found reduced expression of genes in cells subjected to the mechanical forces.

_{Source: Chowdhury et al. 2009. Material properties of the cell dictate stress-induced spreading and differentiation in embryonic stem cells. Nature Materials Online 18 October 2009. doi:10.1038/nmat2563.}

One approach to studying regenerative medicine is to learn more about telomeres, the segments of DNA at the ends of eukaryotic chromosomes that form structures with proteins and help regulate cell replication. Most cells use an enzyme called telomerase to rebuild telomeres when they become shortened or damaged, while some organisms use homogenous recombination. Certain human cancer cell lines have been found to have the capacity for homogenous recombination, but for reasons yet unknown, human cells seem to prefer telomerase. Budding yeast are capable of both processes, providing a perfect model for studying how each works. Using this model, Chen et al. (2009) have discovered that while recombination provides stability to the telomeres, it also shortens the replicative lifespan of the cell line, giving a possible selective advantage to cells that utilize telomerase.

The awarding of the Nobel Prize in Medicine last week, to a scientist who pioneered telomere research, exemplifies the importance of research such as this in areas such as epigenetics, cancer, and stem cell research.

_{Source: Chen, X.F. et al. 2009. Telomere recombination accelerates cellular aging in Saccharomyces cerevisiae. PLoS Genetics, June 2009.}

Until recently, much of genetic research has been directed towards determining the sequences of DNA that code for proteins. Little was known about non-coding regions, although these played an important role in the human genome project.

CpG islands are regions of non-coding DNA, where the number of cytosine and guanine residues is greater than 50% (the remainder consisting of adenine and thymine). These areas of DNA are unmethylated and often found near the 5' ends of genes. They often overlap the promoter region of genes and may even extend into areas where transcription starts. Because of this, and their unique sequences, they make useful tools for gene sequencing and were used in the human genome sequencing project in a process called CpG island tagging.

CpG islands are now being studied for another reason. Although the human genome has been sequenced, we still don't know everything about the gene sequences of origins of replication (ORIs), the starting points from which DNA strands are copied. It appears that a large percent of ORI sequences may lie within GC-rich regions of DNA, and often close to CpG islands. Deciphering the details of where ORIs are found and how they control replication and chromatin formation is part of the study of epigenetics.