10 Awesome Topics in Biology – Part I

In modern Biology, there are some research topics and techniques that are particularly interesting, either because they wouldn’t be conceivable at any other time in history or because they have a strong creative component. Here we present the ten topics that have amazed us the most. We prefer not to numerate them, because we feel that there’s no such thing as a hierarchy in awesomeness.

Here are the first five:

  • Synthetic Biology

A whole new discipline that is continuously growing and generating great results, from synthetic genetic circuits and metabolic pathways to complete working genomes.

By using synthetic biological parts and circuits as tools, Synthetic Biology intends to hack cellular processes and, by tinkering with them, to gain information on the behavior of its natural constituents.

Some nice links:

Ron Weiss thesis (a really good reference about the quantitative part of Synthetic Biology and synthetic gene circuits).
-Some reviews:
a. Heinemann and Panke, (2006), Synthetic biology—putting engineering into biology
b. Ruder, Lu and Collins, (2011), Synthetic Biology Moving into the Clinic
c. Neumann and Neumann-Staubitz, (2010), Synthetic biology approaches in drug discovery and pharmaceutical biotechnology
d. Benner and Sismour, (2005), Synthetic Biology
e. Andrianantoandro, Basu, Karig and Weiss, (2006) Synthetic biology: new engineering rules for an emerging discipline
iGEM main page

  • Metagenomics

Most of the microorganisms out there in the environment cannot be grown in the lab. They may hold a great deal of biotechnologically important functions, but we cannot directly use them.

However, one indirect approach is Metagenomics.

It basically means to take environmental samples from places where one expects to find interesting microorganisms, to process those samples and get the DNA out of all the microorganisms present; after sequencing this collective pool of DNA, one can look for sequences similar to useful, already annotated genes or can construct genetic libraries from the sequence fragments and screen for a particular function.

The are actually many ways to get information out a metagenomic DNA sample, those are only two of them. The cool thing is that one no longer has to find the growth conditions for each microorganism to find useful genes in an environmental sample.

Some nice links are:

JCVI Sorcerer II Expedition (the largest metagenomic expedition to date web page)
PLoS Ocean Metagenomics Collection
-Genomes online database (GOLD) metagenomic studies collection
GOLD genome earth (you can see here the sampling sites for the metagenomic projects registered in GOLD)
-Reviews:
a. Handelsman, (2004), Metagenomics: Application of Genomics to Uncultured Microorganisms

b. Riesenfeld, Schloss and Handelsman, (2006), Metagenomics: Genomic Analysis
of Microbial Communities
c. Daniel, (2005), The metagenomics of soil
d. Streit and Schmitz, (2004), Metagenomics – the key to the uncultured microbes

  • DNA origami

Imagine the possibility of making DNA strands to form shapes like triangles, stars and smiling faces. Even more, if you could shape DNA however you wanted, you could also make nanomaterials and nanomachines.

Well, that is actually possible! By using some scaffolds and relying on base-pairing interactions, DNA strands can be used to construct such shapes. The technology is dubbed “DNA origami” and has been an active research field since 2006.

Some nice links are:

Paul W. K, Rothemund web page (the actual inventor of DNA origami; he works at Caltech and has also done some TED talks, heres one and the other one).
CaDNAno (a free DNA origami designing tool).
Douglas, Bachelet and Church, (2012), A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads (a paper about DNA origami nanobots that deliver anticancer drugs).

  • Directed evolution

Directed evolution is, in principle, the artificial variation and selection of biological functions. Although it could be regarded as a division of Protein Engineering, we think that its characteristics makes it deserve a mention of its own.

Let’s go for the whole story.

There are two basic conditions for the evolution of a system: mutation and a selective pressure. If a system adapted to a certain environment is suddenly changed to another one, it will most likely not continue working unless it has a buffer mechanism that allows it to cope with the new conditions.

In living organims populations, this buffer mechanism would be provided by all those organisms that harbor some mutations in their genes that gives place to phenotypic diversity -from macroscopic features to biochemical ones- in the population; its diversity will help the population to cope with environmental challenges because even when some individuals may die, some others will take advantage of their mutations to survive.

Now, if we already know what a gene does and we somehow relate its function to a selectable feature, we could reproduce the natural process of evolution by artificially inducing mutations in that gene in the whole population -think about creating a mutation library with a regular directed mutagenesis procedure- and then exposing this diverse population to different conditions. This selectable feature does not need to mean “a feature that improves survival chances” because it can just be a signal detected by artificial instruments!

Think about an enzyme that transforms a certain substance; if this reaction is coupled to the release of a tractable signal, then we could screen our mutant library for the best performing variants.

Directed evolution is particularly interesting for improving already existing enzymes, but also to find and improve new functions with protein domain shuffling methods.

Here are some nice links for further reading:
Optimizing non-natural protein function with directed evolution
Biocatalyst development by directed evolution

  • Pharmacogenomics

Pharmacogenomics could be defined as the study of the relationships between a set of genetic variants and the response to a drug, with a global genomic focus and without having a priori assumptions for any particular gene (which is what differentiates it from Pharmacogenetics, a branch that deals with individual genes and their effect with drug response).

Some drug response phenoty have a known genetic component, but for others, this component remains to be discovered; furthermore, the underlying genetic component for the response to some drugs could be best described by the interaction of many components. How can we discover implicated genes and gene interactions?

To discover this interactions and also to discover other clinically relevant gene variants in a population, different approaches can be followed, among which Genome Wide Association Studies are particularly interesant.

With this new information, new drug targets can be discovered and medical practice could move more and more towards personalized medicine; clinical trials may also benefit from the information about the genetic constitution of their participants.

Some nice links for further reading are:
PharmGKB (a database of knowledge on Pharmacogenomics)
-Reviews:
a. Evans and Relling, (1999), Pharmacogenomics: Translating Functional Genomics into Rational Therapeutics
b. Weinshilbourn and Wang, (2006), Pharmacogenetics and Pharmacogenomics: Development, Science, and Translation
c. Nature article series on GWAS

 See the next five topics!

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