The lac Operon Explained [Updated]

Click to enlarge Photo: NIH 

The lac operon is a favorite of microbiology and biology textbooks, used to explain transcription, regulation, and catabolism. Here's my quick synopsis of the regulation involved, making sure the cell only transcribes genes that encode lactose-eating enzymes only when it is physiologically necessary. But first, a GENETICS crash course in biology:

An operon is a group of genes transcribed as a single unit. It's like buying Orange Box. There's five separate games, but they're all purchased at once in a neat box. The same thing with an operon. If the operon is ON, you get all of the genes activated. If the operon is OFF, none of the genes are activated.

RNA polymerase is a protein that reads DNA molecules in the cell to make RNA. This RNA is then read again by ribosomes to direct the synthesis of specific proteins..

Reader's Responses...

For the past week, I've been reading every single comment left on my blog. I've had to delete a few, but most of them were encouraging, funny, and informative. Here's some of the comments you've left me the past few days.

Stem Cell Restrictions Lifted

New court ruling was filed today, issued by Chief Judge Royce Lamberth of the Federal District Court for the District of Columbia. allowing the United States government to continue financing stem cell research for cures for diseases such as Alzheimer's and Parkinson's over public comments on the destruction of embryonic stem cells. The full court ruling is available here Dr. Shirley vs. Sebelius et al. (.pdf format). It's a major victory for science today but there's a lot of public misconception about what stem cells actually are and how human embryos are involved. Let's do a quick overview before we go into the politics of it, shall we?

Stem cells can become any sort of cell in our body.

Every cell in our body is a descendant from a pool of unspecialized cells in the human embryo. Human embryonic stem cells grow, divide, and transform into to every cell in our body. Thus, they have the potential to act as the raw material for repairing damaged tissue affected by injury or disease. As much as these hESCs hold promise for the future of medicine, they are not identical genetic matches with their recipients, making it very likely that the hESCs will trigger an immune response against them.

hESCs are one type of three different cells, the other two being adult stem cells and induced stem cells. hESCs are produced via "derivation," a process which yields "lines" that replicate indefinitely for use in scientific research. In contrast to hESCs, which can become any cell in the body, adult stem cells are limited to only producing certain types of special cells. The third type is the induced stem cell, where viruses are used to force adult cells into pluripotency. By taking cells from an intended recipient and inserting 3-4 genes into it, scientists can reprogram the cell so that its development is reversed, and it becomes similar to a hESC. Not only can induced stem cells become any cell type in the body like hESCs, they do not trigger an immune response because they are a precise genetic match to their recipient. By coaxing adult stem cells to behave more like embryonic cells and thus restoring pluripotency, the limitation on which tissues can be formed from adult cells is circumvented. Despite this breakthrough, one of the genes inserted in the process of induction is associated with cancer, and there are no methods as of now for targeted recombination. The gene is inserted into the genome (the DNA) at random, which presents risks. Some progress has been made, with one paper using transposons from insects to put in and subsequently remove the carcinogenic gene from the genome.

The National Institute of Health has recognized the promise that stem cells hold for medicine, and "believes that it is important to simultaneously pursue all lines of research."

However, research's progress is hindered by fierce political debate in Washington, with politicians arguing over the fate of these unspecialized, pluripotent cells for the past 60 years. Ever since stem cells were discovered, the debate has been fierce, as there are many issues involved, from the legality of stem cell research, to the tax dollars that it requires, to the ethical issues involved with derivation (which destroys the embryo). Take a look at the Dickey-Wicker amendment, enacted yearly since its introduction in 1996, which states:

(1) the creation of a human embryo or embryos for research purposes; or

(2) research in which a human embryo or embryos are destroyed, 

discarded, or knowingly subjected to risk of injury or death  greater 

than that allowed for research on fetuses in utero under 45 CFR 

46.204(b) and section 498(b) of the Public Health Service Act (42 

U.S.C. 289g(b)).

This amendment defines an "embryo" as “any organism, not protected as a human subject under 45 CFR 46 as of the date of the enactment of this Act, that is derived by fertilization, parthenogenesis, cloning, or any other means from one or more human gametes or human diploid cells.”

NIH subsequently received a memo from a government attorney, Harriet S. Rabb, stating embryonic stem cells “are not a human embryo” as defined by the Amendment. Ms. Rabb states stem cells “are not even precursors to human organisms,” because stem cells can only develop into different cell types within the human body, while embryos can potentially develop into human organisms.

More than 10 years later, President Obama has issued this memorandum (whitehouse.gov), stating that the government will give more power to the scientists in terms of in what direction research is to take. In Obama's Executive Order No. 13,505, it states that the “[NIH] may support and conduct responsible, scientifically worthy stem cell research, including human embryonic stem cell research, to the extent permitted by law."

"President Obama is committed to supporting responsible stem cell research and today's ruling was another step in the right direction," said his deputy senior adviser Stephanie Cutter.

With all of this in mind, do you support stem cell research? Do you think induced stem cells hold promise, or disagree with that, and believe that they "hold great peril," in the words of President Bush? Make your voice heard and comment below.

Origin of Life?

courtesy of dailygalaxy.com

There's a fascinating article in Nature (here's the article, courtesy of the University of Texas) on how life started on Earth, and the evidence in rRNA that suggests it came from deep hydrothermal vents in the ocean. The article here focuses on the similarities between the metabolism of autotrophs and the geochemical reactions that take place in the vents. The reactive gases, dissolved elements, the pH, and thermal gradients at the vents are suitable for the development of life. Given that the same type of environment was very common in early Earth's oceans, it is likely that the microbes that thrive at the vents could be closely related to the first microbes on Earth, despite oxic conditions and carbonate chimneys in modern vents. The vents in early Earth were anoxic, and were FeS-rich in comparison. Anaerobic methane-oxidizing microbes' biological pathways were compared to the geochemical process of serpentinization, where water and bicarbonate reduce Fe2+ in hydrothermially altered mantle rock to produce serpentine and hydrogen gas. Hydrogen gas is an electron source that can, in turn, reduce carbon dioxide to methane in a process similar to the biochemical pathways of local methane-oxidizing microbes. This comparison is important because if life did arise from systems like LCHF, serpentinization could have been an evolutionry precursor to the first biochemical pathways. To support the possibility of life originating at LCHF-like systems, the authors mentioned that the pH and thermal gradients at the LCHFs would allow high concentration of biological precursors to form, and that they could be used to explain the origins of chemiosmotic coupling in modern autotrophs.

In contrast to the anoxic oceans of the Hadean era, today's oceans have plenty of oxygen. Thus the chemical of composition of the LCHFs and the vents would be different from the oceans of early Earth. The presence of oxygen means very different microbes would exist then, compared to now. How do aerobic microbes in the hydrothermal vents, figure in finding the origins of life? Are they of any special interest, or should further research focus on methanogens only? How did lipid bilayers, a sure prerequisite for life, come about? Most of the compounds discussed in the article are very simple and small.

Why Cancer Is Going To Be Difficult To Beat

As homemakesgames said in the last QOTD, cancer is very complicated. There are so many different types of cancers. There is not going to be a single cure for all cancers. Cancer is not a single mutation in our cells, it's a whole bunch of possible mutations that leave the cell unable to receive feedback from its environment or properly repair damaged DNA. Cancerous cells grow blood vessels to bring nutrients in from surrounding, healthy tissue, disrupting them. Not only do they quickly invade healthy tissue, they have figured out a way to cheat death. Ignoring all kinds of growth inhibitors from the rest of the body, cancerous cells circumvent limitations on how many times its DNA can be copied. They have figured out ways to deactivate programmed limits in its own lifespan. This process can occur in many ways, which makes finding a common cure near impossible. If there is only one thing all cancers have in common, it is that, without treatment, their host cannot sustain them.

No Science Sunday: Squid and Soy Sauce Edition

For some explanation of my last paper, the aberrant RNA results in chloride channels that don't work properly in the muscle membrane of the genetically altered mice. Ion channels are very important in muscles. Electrochemical gradients caused by ion concentration makes action potential in muscles possible. Not directly related to the article at all, but an interesting video nonetheless, here's what happens when people pour a lot of sodium over a squid.

Ion pumps maintain the ion gradient across the membrane in a living organism necessary for coordinated movements in the muscle. In the video, the high sodium content of the soy sauce briefly increases the extracellular concentration of sodium  Naturally, these want to diffuse across the membrane to try to reach a state of equilibrium between the inner and outer sections of the membrane. The electrochemical gradient depolarizes the squid neurons, generating action potentials.

In the video, this has less to do with the pumps than it does with the gradient of sodium ions. Still, it's a good illustration of the importance of ions and the pumps which regulate them. 

Myotonic Dystrophy and Aberrant Splicing of RNA

Myotonic dystrophy is an autosomal dominant disease. It involves the electrical instability of muscle tissue, resulting in conductive heart defects, cataracts in the eye, weak muscles, and rapid discharges that make coordinated movement extremely difficult. Skeletal muscle depends on membrane action potential. When there aren’t enough ClC-1 channels in the membrane of skeletal muscle cells, Cl- conductance is reduced. Cl- is unable to stabilize the resting membrane potential, resulting in erratic contractions and delayed muscle relaxation.


There are two types of, DM type 1 is caused by 50 to >3000 CTG repeats in the 3’ untranslated region of the DMPK gene on chromosome 19, and DM type 2 is caused by 75 to 11,000 CCTG repeats in the first intron of the ZNF9 gene on chromosome 3. The repeats are amplified after every generation, and the severity of the symptoms of DM1 and DM2 are proportional to the size of the repeats. Most troublesome is the autosomal dominant nature of the disease; even if just one parent has the disease, 50% of the children will get the disease. How do microsatellite repeats in a region that does not code for protein can cause a dominantly inherited disease?


MBNL proteins, encoded for by the MBNL1, MBNL2, and MBNL3 genes, have been shown to bind to expanded CUG repeats on the DMPK and ZNF9 transcripts and accumulate in the nucleus in vivo. Does the sequestering of MBNL proteins in the nucleus contribute to the development of DM and change ClC-1 splicing?

Question of the Day: Selective Breeding Of Foxes and Dogs

In NOVA's documentary Dogs Decoded, scientists attempt to breed out aggressive behavior in wild foxes in order to domesticate them like dogs. They selectively bred the foxes (the most calm of each litter were bred with each other, and the most aggressive with each other) and after only 8 generations, they successfully domesticated   the calmer foxes. They noticed that the foxes that were bred to be calmer also had shorter legs, whiter hair, while the foxes bred based on aggression were darker, had longer legs, and bushy tails.



When dogs were domesticated from grey wolves, they also had a physical change: a shorter snout, shorter legs, and a sloping forehead. These myriad of changes came with changes in their behavior. For example, dogs intuitively know how to read human faces, for example. Dogs play fetch and respond to pointing. Wolves do not have any of these abilities, even when raised from birth in a human household and trained like a dog. Even within the dog species, each breed has its unique temperament to go along with its unique physical traits. The question of the day is: Do you think physical characteristics are intrinsically linked to mental characteristics?


Dogs Decoded:
http://www.pbs.org/wgbh/nova/nature/dogs-decoded.html

Photons, Time, and the Speed of Light

Time and the speed of light have a very close relationship. The speed of light in a vacuum moves at a constant rate at 186.000 miles per second, yet time does not. In fact, time dilates as you move faster.

t' = factor of time dilation, t = time, v = how fast you're going, c = speed of light

In the reference frame of a photon, all distances parallel to the direction of propagation become zero due to Lorentz contraction. (Read the first link which explains space contraction.) Because space contracts infinitely, the distance a photon travels, from its perspective, is zero. The zero distance is covered in zero time. In the reference frame of the photon, every photon of light comes into being at a single point, then instantly vanishes at the same point.
 

In other words, a photon of light connects its emitter and its absorber instantaneously. However, from our perspective that photon is emitted at the speed of light and travels at that speed until it is absorbed, and the time interval from emission to absorption, from our perspective, could be near zero to the age of the universe.

Why did I ask that question? I was reading a book on Einstein (or by Einstein?) and it talked about the twin paradox. There's a set of twins, and one of the twins goes on a spaceship with a clock onboard while his twin stays on Earth. The spaceship then orbits around the Earth near the speed of light for 30 seconds, according to the clock on the spaceship. When the spaceship lands, the twin on the spaceship meets his twin, but his twin who stayed on Earth has aged and is an old man! This is to illustrate how time slows down, or dilates, the faster you move in the reference frame of a stationary observer. So I had a question: If the faster you go, the slower time moves, and the speed of light is the "speed limit" in the universe, does that mean time stands still for a photon of light?
 

Eintein's paper in 1905: http://www.fourmilab.ch/etexts/einstein/specrel/www/

The first half deals with time dilation and space contraction. Time expands from the viewpoint of the stationary observer, and space contracts from the viewpoint of the moving observer! We'll get to Lorentz contraction later. It doesn't directly answer the question.

Informative webpage on time and the speed of light: http://www.costellospaceart.com/html/time_and_the_speed_of_light.html

Question of the Day

Does time stand still for a photon?


This question will be answered tomorrow!

Why genetics is so fascinating to me...

It's amazing what we can do with genetic manipulation. We can see how closely two organisms are related genetically, without having to rely on physical similarities, which can be quite misleading. We can express proteins from one living thing and express it in another, even in specific tissues. For example, fish can make protein X on the linings of their gills. It is possible to have protein X be expressed in just the brain of a mouse.


Genetics itself determines everything, from our hair color, to the tameness of dogs versus wolves, to the probability of us having cancer, or children with congenital defects. By manipulating genetic material, we can alter what makes us us. I think that is absolutely remarkable, and I hope you do, too.

Stability and Morphology of Gold Nanoisland Arrays Generated from Layer-by-Layer Assembled Nanoparticle Multilayer Films: Effects of Heating Temperature and Particle Size

http://www.ncbi.nlm.nih.gov/pubmed/21625329


It's not molecular genetics, but...


I am going to write a small paper and summary on this paper within the week. Read it before and let's discuss it!


UPDATE: I'm waiting until I can get the article from my professor. It will be around 2 months from now.