In our increasingly transparent lives, scientists are beginning to perfect the ultimate transparency - peering into the goings-on inside the most fundamental components of our lives: our own cells. While the transparency that we currently live with due to social media's pervasiveness (invasiveness?) in our daily lives can be seen as both a benefit and a drawback, this form of transparency is considerably more awe-inspiring and will ultimately lead to major new discoveries related to human diseases and their treatment.
In an extremely elegant piece of work, chemists at MIT have combined two stalwarts of biochemical analysis, the electron (or fluorescent) microscope and the mass spectrometer, to create a new tool that can actually allow determination of the co-localization of as many as hundreds (if not thousands) of proteins in a particular subcellular location, which will ultimately change our knowledge on various cellular processes.
Previous studies were able to do this for maybe 30-40 proteins in a cell, but in the recent study published online in the prestigious journal "Science" (Jan. 31 edition), as many as 500 proteins were mapped in the matrix of the mitochondria, our cell's very own powerhouse that produces our energy and performs many biosynthetic reactions.
“That’s a holy grail for biology, to be able to get spatially and temporally resolved molecular maps of living cells,” said Alice Ting, the Ellen Swallow Richards Associate Professor of Chemistry at MIT.
Without wanting to get too technical for a layperson audience, effectively such studies were previously limited by the number of proteins that could be tagged without overloading the readout and losing discrimination. Additionally, techniques were messy because the cell had to be opened to allow mass spectrometry analyses of the cell's contents, which meant mixing occurred and spatial data could not be reliably obtained.
This development involves tagging of all the proteins in a chosen location, in advance of making the cell permeable (or leaky), which thus allows spatial location information to be recorded before taking the cell contents for mass spec examination. This means that a reconstruction of the contents at a given moment can be performed using the location tags that labeled the proteins inside a functioning living cell. It is a spectacularly exciting step, and one which will surely necessitate some rewriting of our beloved old standard biochemistry text books!
In fact, this is already the case. The researchers found that an enzyme required for synthesis of the "heme" component of hemoglobin (which carries oxygen in our blood) is not located where scientists thought it was, and its presence in the matrix now implies that there are heretofore unknown transporters that bring heme precursors to the mitochondrial matrix.
"Just relocalizing things causes people to have to rethink these biosynthetic pathways and how intermediates are moved around.. The molecular understanding of that pathway has to be rewritten now, based on our data." said Ting.
The possibilities are endless, and of course, one of the most fascinating things will be comparison of normal cells and their various subcellular protein players at a given location or organelle, with abnormal cells such as cancer cells or cells from diseased tissues. We will unquestionably gain an abundance of new information about the normal and diseased cell phenotypes using this new tool, and at some point or another such data will lead to a better therapeutic intervention of human disease.
If there's one thing I can say about science, it sure ain't boring. As much as electronic technology and the new media they run (well, more and more it is social media that runs the device/runs our lives!) have changed our lives in an interesting way, this type of scientific advance that allows peering down into and inside of the living cell is just explosively exciting by comparison! Spoken like a true scientist, I guess!
It's a small difference between social media's capacity to run one's life or ruin it. What a difference an "i" makes?! But in a sense, this new breakthrough will allow a form of cellular social media to be elucidated. Instead of seeing a diagram about how one is connected to a whole bunch of contacts (direct or indirect) on Facebook, Twitter or Google+, and various interactions between them all, we will now be able to look at the connections (direct and indirect) between a whole slew of proteins in various cellular compartments. We will have a much greater understanding of who interacts with who, and who stays away.
Hmm, so maybe cellular social media isn't so bad after all? It all depends which type of cellular turns you on, I suppose! ;)
One of the hardest things about science and its pursuit is that one rarely gets to stick around long enough to see the massive transformative breakthroughs that answer the big questions. I can only imagine the smiles of legendary Dutch scientist Anton van Leeuwenhoek (who died in 1723) at being able to see this discovery, having been the pioneer who first created the microscope and saw aspects of our life too small to see with the human eye. In his day, it was exciting to see mircoorganisms or blood flow in capillaries, and here we are today talking about "seeing" hundreds of macromolecular (big molecules) proteins interacting at a subcellular level. Amazing!
I suppose I shall just have to work harder at discovering the elusive elixir of life, a potent life-extending potion or pill, so that we all may get a chance to stick around longer and be able to witness where medicine is going to race to in the next 100 years. Speaking of potent potions, I am done and it's time for a mug of that intense Peruvian dark roast "Emperor's Blend"! ;) - Kevin Mc
[PS - Due to a combination of personal and professional reasons, I was on a form of hiatus for most of January, 2013, but in response to various queries that came in, I want to underline the fact that I am back, and will be blogging (on a perhaps less frequent basis) at least weekly from now on. Thanks for sticking with me, and thanks to those who dropped me a note demanding that I post some blogs as I was unusually quiet in January. Be careful what you wish for! ;) ]
[PS - Due to a combination of personal and professional reasons, I was on a form of hiatus for most of January, 2013, but in response to various queries that came in, I want to underline the fact that I am back, and will be blogging (on a perhaps less frequent basis) at least weekly from now on. Thanks for sticking with me, and thanks to those who dropped me a note demanding that I post some blogs as I was unusually quiet in January. Be careful what you wish for! ;) ]
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