Tag: rna

Neuroscientists Transfer “Memories” from One Snail to Another: A Christian Perspective on Engrams

neuroscientiststransfer

BY FAZALE RANA – SEPTEMBER 26, 2018

Scientists from UCLA recently conducted some rather bizarre experiments. For me, it’s these types of things that make it so much fun to be a scientist.

Biologists transferred memories from one sea slug to another by extracting RNA from the nervous system of a trained sea slug and then injecting the extract into an untrained sea slug.1 After the injection, the untrained sea snails responded to environmental stimuli just like the trained ones, based on false memories created by the transfer of biomolecules.

Why would researchers do such a thing? Even though it might seem like their motives were nefarious, they weren’t inspired to carry out these studies by Dr. Frankenstein or Dr. Moreau. Instead, they had really good reasons for performing these experiments: they wanted to gain insight into the physical basis of memory.

How are memories encoded? How are they stored in the brain? And how are memories retrieved? These are some of the fundamental scientific questions that interest researchers who work in cognitive neuroscience. It turns out that sea slugs belonging to the group Aplysia(commonly referred to as sea hares) make ideal organisms to study in order to address these questions. The fact that we can gain insight into how memories are stored with sea slugs is mind-blowing and indicates to me (as a Christian and a biochemist) that biological systems have been designed for discovery.

Sea Hares

Sea hares have become the workhorses of cognitive neuroscience. This creature has a nervous system that’s complex enough to allow neuroscientists to study reflexes and learned behaviors, but simple enough that they can draw meaningful conclusions from their experiments. (By way of comparison, members of Aplysia have about 20,000 neurons in their nervous systems compared to humans who have 85 billion neurons in our brains alone.)

Toward this end, neuroscientists took advantage of a useful reflexive behavior displayed by sea hares, called gill and siphon withdrawal. When these creatures are disturbed, they rapidly withdraw their delicate gill and siphon.

The nervous system of these creatures can also experience sensitization, which is learned by repeated exposure to stimuli, resulting in an enhanced and broad response by the nervous system to stimuli that are related—say, stimuli that connote danger.

What Causes Memories?

Sensitization is a learned response that is possible because memories have been encoded and stored in the sea hares’ nervous system. But how is this memory stored?

Many neuroscientists think that the physical instantiation of memories (called engrams) reside in the synaptic connections between nerve cells (neurons). Other neuroscientists hold a differing view. Instead of being mediated by cell-cell interactions, others think that engrams form within the interior of neurons, through biochemical events that take place within the cell nucleus. In fact, some studies have implicated RNA molecules in memory formation and storage.2 The UCLA researchers sought to determine if RNA plays a role in memory formation.

Memory Transfer from One Sea Hare to Another

To test this hypothesis, the researchers sensitized sea hares to painful stimuli. They accomplished this feat by inserting an electrode in the tail regions of several sea hares and delivering a shock. The shock caused the sea hares to withdraw their gill and siphon. After 20 minutes, they repeated the shock protocol and continued to do so in 20-minute intervals five more times. Twenty-four hours later, they repeated the shock protocol. By this point, the sea hare test subjects were sensitized to threatening stimuli. When touched, the trained sea hares would withdraw their gill and siphon for nearly 1 minute. Untrained sea hares (who weren’t subjected to the shock protocol) would withdraw their gill and siphon when touched for only about 1 second.

Next, the researchers sacrificed the sensitized sea hares and isolated RNA from their nervous system. Then they injected the RNA extracts into the hemocoel of untrained sea hares. When touched, the sea hares withdrew their gill and siphon for about 45 seconds.

To confirm that this response was not due to the injection procedure, they repeated it by injecting RNA extracted from the nervous system of an untrained sea hare into untrained sea hares. When touched, the gill and siphon withdrawal reflex lasted only about 1 second.

neuroscientists-transfer-memories-from-one-snail-to-another

Figure: Sea Hare Stimulus Protocol. Image credit: Alexis Bédécarrats, Shanping Chen, Kaycey Pearce, Diancai Cai, and David L. Glanzman, eNeuro 14 May 2018, 5 (3) ENEURO.0038-18.2018; doi:10.1523/ENEURO.0038-18.2018.

The researchers then applied the RNA extracts from both trained and untrained sea hares to sensory neurons grown in the lab. The RNA extracts from the trained sea hares caused the sensory neurons to display heightened activity. Conversely, the RNA extracts from the untrained sea hares had no effect on the activity of the cultured sensory neurons.

Finally, the researchers added compounds called methylase inhibitors to the RNA extracts before injecting them into untrained sea hares. These inhibitors blocked the memory transfer. This result indicates that epigenetic modifications of DNA mediated by RNA molecules play a role in forming engrams.

Based on these results, it appears that RNA mediates the formation and storage of memories. And, though the research team does not know which class of RNAs play a role in the formation of engrams, they suspect that micro RNAs may be the biochemical actors.

Biomedical Implications

Now that the UCLA researchers have identified RNA and epigenetic modifications of DNA as central to the formation of engrams, they believe that it might one day be possible to develop biomedical procedures that could treat memory loss that occurs with old age or with diseases such as Alzheimer’s and dementia. Toward this end, it is particularly encouraging that the researchers could transfer memories from one sea hare to another. This insight might even lead to therapies that would erase horrific memories.

Of course, this raises questions about human nature—specifically, the relationship between the brain and mind. For many people, the fact that there is a physical basis for memories suggests that our mind is indistinguishable from the activities taking place within our brains. To put it differently, many people would reject the idea that our mind is a nonphysical substance, based on the discovery of engrams.

Engrams, Brain, and Mind

However, I would contend that if we adopt the appropriate mind-body model, it is possible to preserve the concept of the mind as a nonphysical entity distinct from the brain even if engrams are a reality. A model I find helpful is based on a computer hardware/software analogy. Accordingly, the brain is the hardware that manifests the mind’s activity. Meanwhile, the mind is analogous to the software programming. According to this model, hardware structures—brain regions—support the expression of the mind, the software.

A computer system needs both the hardware and software to function properly. Without the hardware, the software is just a set of instructions. For those instructions to take effect, the software must be loaded into the hardware. It is interesting that data accessed by software is stored in the computer’s hardware. So, why wouldn’t the same be true for the human brain?

We need to be careful not to take this analogy too far. However, from my perspective, it illustrates how it is possible for memories to be engrams while preserving the mind as a nonphysical, distinct entity.

Designed for Discovery

The significance of this discovery extends beyond the mind-brain problem. It’s provocative that the biology of a creature such as the sea hare could provide such important insight into human biology.

This is possible only because of the universal nature of biological systems. All life on Earth shares the same biochemistry. All life is made up of the same type of cells. Animals possess similar anatomical and physiological systems.

Most biologists today view these shared features as evidence for an evolutionary history of life. Yet, as a creationist and an intelligent design proponent, I interpret the universal nature of the cell’s chemistry and shared features of biological systems as manifestations of archetypical designs that emanate from the Creator’s mind. To put it another way, I regard the shared features of biological systems as evidence for common design, not common descent.

This view leads to the follow-up rebuttal: Why would God create using the same template? Why not create each biochemical system from scratch to be ideally suited for its function? There may be several reasons why a Creator would design living systems around a common set of templates. In my estimation, one of the most significant reasons is discoverability. The shared features of biochemical and biological systems make it possible to apply what we learn by studying one organism to all others. Without life’s shared features, the discipline of biology wouldn’t exist.

This discoverability makes it easier to appreciate God’s glory and grandeur, as evinced by the elegance, sophistication, and ingenuity in biochemical and biological systems. Discoverability of biochemical systems also reflects God’s providence and care for humanity. If not for the shared features, it would be nearly impossible for us to learn enough about the living realm for our benefit. Where would biomedical science be without the ability to learn fundamental aspects of our biology by studying model organisms such as yeast, fruit flies, mice—and sea hares?

The shared features in the living realm are a manifestation of the Creator’s care and love for humanity. And there is nothing bizarre about that.

Resources

Endnotes

  1. Alexis Bédécarrats et al., “RNA from Trained Aplysia Can Induce an Epigenetic Engram for Long-Term Sensitization in Untrained Aplysia,” eNeuro 5 (May/June 2018): e0038-18.2018, 1–11, doi:10.1523/ENEURO.0038-18.2018.
  2. For example, see Germain U. Busto et al., “microRNAs That Promote Or Inhibit Memory Formation in Drosophila melanogaster,” Genetics 200 (June 1, 2015): 569–80, doi:10.1534/genetics.114.169623.
Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2018/09/26/neuroscientists-transfer-memories-from-one-snail-to-another-a-christian-perspective-on-engrams

Ribosomes: Manufactured by Design, Part 2

ribosomesmanufacturedbydesign

BY FAZALE RANA – NOVEMBER 8, 2017

“I hope there are no creationists in the audience, but it would be a miracle if a strand of RNA ever appeared on the primitive Earth.”1

Hugh Ross and I witnessed the late origin-of-life researcher, Leslie Orgel, make this shocking proclamation at the end of a lecture he presented at the 13th International Conference on the Origin of Life (ISSOL 2002).

Orgel was one of the originators of the RNA world hypothesis. And because of his prominence in the origin-of-life research community, the conference organizers granted Orgel the honor of opening ISSOL 2002 with a plenary lecture on the status of the RNA world hypothesis. During his presentation, Orgel described problem after problem with the leading origin-of-life explanation, reaching the tongue-in-cheek conclusion that it would require a miracle for this evolutionary scenario to yield RNA, let alone the first life-forms. (For a detailed discussion of the problems with the RNA world hypothesis, see my book Creating Life in the Lab.)

Despite these problems, many origin-of-life researchers—including Leslie Orgel (while he was alive)—remain convinced that the RNA world scenario must be the explanation for the emergence of life via chemical evolution. Why? For one key reason: the intermediary role RNA plays in protein synthesis.

The RNA World Hypothesis

The RNA world hypothesis posits that biochemistry was initially organized exclusively around RNA and only later did evolutionary processes transform the RNA world into the familiar DNA-protein world of contemporary organisms. If this model is correct, then the DNA-protein world represents the historically contingent outworking of evolutionary history. To put it another way, contemporary biochemistry has been cobbled together by unguided evolutionary forces and the role RNA plays in protein synthesis is an accidental outcome.

The discovery of ribozymes in the 1980s provided initial support for the RNA world scenario. These RNA molecules possess functional capabilities, behaving just like enzymes. In other words, RNA not only harbors information like DNA, it also carries out cellular functions like proteins. Origin-of-life researchers take RNA’s dual capacities as evidence that life could have been organized around RNA biochemistry. These same researchers presume that evolutionary processes later apportioned RNA’s twofold capabilities between DNA (information storage) and proteins (function). Origin-of-life researchers often point to RNA’s intermediary role in protein synthesis as evidence for the RNA world hypothesis. Again, RNA’s reduced role in contemporary biochemical systems stands as a vestige of evolutionary history, with RNA viewed as a sort of molecular fossil.

Ribosomes serve as a prime illustration of RNA’s role as a go-between in protein synthesis. As subcellular particles, ribosomes catalyze (assist) the chemical reactions that form the bonds between the amino acid subunits of the proteins. Two subunits of different sizes (comprised of proteins and RNA molecules) combine to form a functional ribosome. In organisms like bacteria, the large subunit (LSU) contains 2 ribosomal RNA (rRNA) molecules and about 30 different protein molecules. The small subunit (SSU) consists of a single rRNA molecule and about 20 proteins. In more complex organisms, the LSU is formed by 3 rRNA molecules that combine with around 50 distinct proteins, and the SSU consists of a single rRNA molecule and over 30 different proteins.

The rRNA molecules function as scaffolding, organizing the myriad ribosomal proteins. They also catalyze the chain-forming reactions between amino acids. In other words, the ribosome is a ribozyme. At the ISSOL 2002 meeting, I heard Orgel adamantly insist that the RNA world hypothesis must be valid because rRNA catalyzes protein bond formation.

Orgel’s perspective gains support considering the inefficiency of ribozymes as catalysts. Protein enzymes are much more efficient than ribozymes. In other words, it seemingly would be better and more efficient to design ribosomes so that proteins catalyzed bond formation between amino acids, not rRNA. This reason convinces origin-of-life researchers that the role rRNAs play in protein synthesis is a haphazard consequence of life’s historically contingent evolutionary history.

But recent work by scientists from Harvard and Uppsala Universities paints a different picture of the compositional makeup of ribosomes, and in doing so, undermines what many origin-of-life researchers believe to be the most compelling evidence for the RNA world hypothesis. These researchers demonstrate that the compositional makeup of ribosomes does not appear to be the accidental outworking of an unguided, contingent process. Instead, an exquisite molecular logic accounts for the composition and structural properties of the protein and rRNA components of ribosomes.2

Is There a Rationale for Ribosome Structure?

As part of their research efforts, the Harvard and Uppsala University investigators were specifically trying to answer several questions related to the composition of ribosomes, including:

  1. Why are ribosomes made up of so many proteins?
  2. Why are ribosomal proteins nearly the same size?
  3. Why are ribosomal proteins smaller than typical proteins?
  4. Why are ribosomes made up of so few rRNA molecules?
  5. Why are rRNA molecules so large?
  6. Why do ribosomes employ rRNA as the catalyst to form bonds between amino acids, instead of proteins which are much more efficient as enzymes?

Ribosomes Make Ribosomes

Before a cell can replicate, ribosomes must manufacture the proteins needed to form more ribosomes—in fact, ribosomes need to manufacture enough proteins to form a full complement of these subcellular complexes. This ensures that both daughter cells have the sufficient number of protein-manufacturing machines to thrive once the cell division process is completed. Because of this constraint, cell replication cannot proceed until a duplicate population of ribosomes is produced.

Ribosome Composition is Optimal for Efficient Production of Ribosomes

As discussed in an earlier blog post, the Harvard and Uppsala University investigators discovered that if ribosomal proteins were large, or if these biomolecules were variable in size, ribosome production would be slow and inefficient. Building ribosomes with smaller, uniform-size proteins represents the faster way to duplicate the ribosome population, permitting the cell replication to proceed in a timely manner. They also determined that the optimal number of ribosomal proteins is between 50 to 80—the number of ribosomal proteins found in nature. In short, the composition of these sub cellular complexes appears to be undergirded by an elegant molecular rationale.

As part of their mathematical modeling study, these researchers also provided an explanation for why ribosomes are made up of large RNA molecules. Because the number of steps involved in rRNA production is fewer than the steps required for protein manufacture, rRNA molecules can be made more rapidly than proteins. This being the case, ribosome production is more efficient when these organelles are built using fewer and larger rRNA molecules as opposed to smaller, more numerous ones.

The research team learned that ribosomes containing more rRNA can be built faster than ribosomes made up of more proteins. This fact helps explain why rRNA operates as the catalytic portion of ribosomes (linking amino acids together to construct proteins), though less efficient as a catalyst than proteins.

These insights also explain the compositional differences among ribosomes found in bacteria, eukaryotic cells, and mitochondria. Bacteria, which typically replicate faster than eukaryotic cells, possess ribosomes that contain proportionally more rRNA and fewer proteins than ribosomes found in eukaryotic cells. Mitochondria—organelles found in eukaryotic cells—possess ribosomes with a much greater ratio of proteins to rRNA than eukaryotic cells. This observation makes sense because ribosomes in mitochondria don’t produce themselves.

It Would Be a Miracle if a Strand of RNA Appeared on the Primitive Earth

An exquisite molecular rationale undergirds the number and size of rRNA molecules in ribosomes and accounts for why the ribosome is a ribozyme. The work of the Harvard and Uppsala University scientists undermines the view that ribosomes were cobbled together as a result of the evolutionary transition from the RNA world to the DNA/protein world. If the presence and role of RNA molecules in ribosomes were simply vestiges of life’s origin out of an RNA world, then there should not be an elegant molecular logic that accounts for ribosome compositions in bacteria and eukaryotic organisms. In other words, it doesn’t appear as if ribosomes are the unintended outcome of an unguided evolutionary process.

This conclusion gains support from earlier work by life scientist Ian S. Dunn. As I wrote about in a previous blog post, Dunn has uncovered a molecular rationale for the intermediary role messenger RNA (mRNA) plays in protein synthesis. Again, it indicates that the intermediary role of RNA molecules in protein synthesis is a necessary design of a DNA/protein world, not a molecular vestige of life’s evolutionary origin that proceeds through an RNA world.

Given these new insights and the intractable problems with the RNA world scenario, I must agree with Leslie Orgel. It would be a miracle if a strand of RNA appeared on the primitive Earth—unless a Creator intervened.

Resources to Dig Deeper

Endnotes

  1. Fazale Rana, Creating Life in the Lab: How New Discoveries in Synthetic Biology Make a Case for the Creator(Grand Rapids, MI: Baker Books, 2011), 161.
  2. Shlomi Reuveni, Måns Ehrenberg, and Johan Paulsson, “Ribosomes Are Optimized for Autocatalytic Production,” Nature 547 (July 20, 2017): 293–7, doi:10.1038/nature22998.
Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2017/11/08/ribosomes-manufactured-by-design-part-2

DNA: Designed for Flexibility

dnadesignedforflexibility

BY FAZALE RANA – AUGUST 17, 2016

Over the years I’ve learned that flexibility is key to a happy and successful life. If you are too rigid, it can create problems for you and others and rob you of joy.

Recently, a team of collaborators from Duke University and several universities in the US discovered that DNA displays unexpected structural flexibility. As it turns out, this property appears to be key to life.1 In contrast, the researchers showed that RNA (DNA’s biochemical cousin) is extremely rigid, highlighting another one of DNA’s unique structural properties that make it ideal as the cell’s information storage system.

To appreciate DNA’s uniquely optimal properties, a review of this important biomolecule’s structure is in order.

DNA

DNA consists of two chain-like molecules (polynucleotides) that twist around each other to form the DNA double helix. The cell’s machinery forms polynucleotide chains by linking together four different sub-unit molecules called nucleotides. DNA is built from the nucleotides: adenosine, guanosine, cytidine, and thymine, famously abbreviated A, G, C, and T, respectively.

In turn, the nucleotide molecules that make up the strands of DNA are complex molecules, consisting of both a phosphate moiety, and a nucleobase (either adenine, guanine, cytosine, or thymine) joined to a 5-carbon sugar (deoxyribose). (In RNA, the five-carbon sugar ribose replaces deoxyribose.)

dna-designed-for-flexibility-1Image 1: Nucleotide Structure

The backbone of the DNA strand is formed when the cell’s machinery repeatedly links the phosphate group of one nucleotide to the deoxyribose unit of another nucleotide. The nucleobases extend as side chains from the backbone of the DNA molecule and serve as interaction points (like ladder rungs) when the two DNA strands align and twist to form the double helix.

dna-designed-for-flexibility-2Image 2: The DNA Backbone

When the two DNA strands align, the adenine (A) side chains of one strand always pair with thymine (T) side chains from the other strand. Likewise, the guanine (G) side chains from one DNA strand always pair with cytosine (C) side chains from the other strand.

When the side chains pair, they form cross bridges between the two DNA strands. The length of the A-T and G–C cross bridges is nearly identical. Adenine and guanine are both composed of two rings and thymine (uracil) and cytosine are composed of one ring. Each cross bridge consists of three rings.

When A pairs with T, two hydrogen bonds mediate the interaction between these two nucleobases. Three hydrogen bonds accommodate the interaction between G and C. The specificity of the hydrogen bonding interactions accounts for the A-T and G-C base-pairing rules.

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Image 3: Watson-Crick Base Pairs

Watson-Crick and Hoogsteen Base Pairing

In DNA (and in RNA double helixes), the base pairing interactions occur at precise locations between the A and T nucleobases and the G and C nucleobases, respectively. Biochemists refer to these exacting interactions as Watson-Crick base pairing. However, in 1959—six years after Francis Crick and James Watson published their structure for DNA—a biochemist named Karst Hoogsteen discovered another way—albeit, rare—that the A and T nucleobases and the G and C nucleobases pair, called Hoogsteen base pairing.

Hoogsteen base pairing results when the nucleobase attached to the sugar rotates by 180°. Because of the dynamics of the DNA molecule, this nucleobase rotation occurs occasionally, converting a Watson-Crick base pair into a Hoogsteen base pair. However, the same dynamics will eventually revert the Hoogsteen base pair to a Watson-Crick pairing. Hoogsteen base pairs aren’t preferred because they cause a distortion in the DNA double helix. For a “naked” piece of DNA in a test tube, at any point in time, about 1 percent of the base pairs are of the Hoogsteen variety.

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Image 4: Watson-Crick and Hoogsteen Base Pairs
Image Credit: Wikimedia Commons

While rare in naked DNA, biochemists have recently discovered that the Hoogsteen configuration occurs frequently when: 1) proteins bind to DNA; 2) DNA is methylated; and 3) DNA is damaged. Biochemists now think that Hoogsteen base pairing is important to maintain the stability of the DNA double helix, ensuring the integrity of the information stored in the DNA molecule.

According to Hashim Al-Hashimi, “There is an amazing complexity built into these simple beautiful structures, whole new layers or dimensions that we have been blinded to because we didn’t have the tools to see them, until now.”2

It looks like the capacity to form Hoogsteen base pairs is a unique property of DNA. Al-Hashimi and his team failed to detect any evidence for Hoogsteen base pairs in double helixes made up of two strands of RNA. When they chemically attached a methyl group to the nucleobases of RNA to block the formation of Watson-Crick base pairs and force Hoogsteen base pairing, they discovered that the RNA double helix fell apart. Unlike the DNA double—which is flexible—the RNA double helix is rigid and cannot tolerate a distortion to its structure. Instead, the RNA strands can only dissociate.

It turns out that the flexibility of DNA and the rigidity of RNA is explained by the absence of a hydroxyl group in the 2’ position of the deoxyribose sugar of DNA and the presence of the 2’ hydroxyl group on ribose sugar of RNA, respectively. The 2’ position is the only structural difference between the two sugars. The presence or absence of the 2’ hydroxyl group makes all the difference. The deoxyribose ring can more freely adopt alternate conformations (called puckering) than the ribose ring, leading to differences in double helix flexibility.

dna-designed-for-flexibility-5

Image 5: Difference between Deoxyribose and Ribose

This difference makes DNA ideally suited as an information storage molecule. Because of its ability to form Hoogsteen base pairs, the DNA double helix remains intact, even when the molecule becomes chemically damaged. It also makes it possible for the cell’s machinery to control the expression of the genetic information harbored in DNA through protein binding and DNA methylation.

It is intriguing that DNA’s closet biochemical analogue lacks this property.

It appears that DNA has been optimized for data storage and retrieval. This property is critical for DNA’s capacity to store genetic information. DNA harbors the information needed for the cell’s machinery to make proteins. It also houses the genetic information passed on to subsequent generations. If DNA isn’t stable, then the information it harbors will become distorted or lost. This will have disastrous consequences for the cell’s day-to-day operations and make long-term survival of life impossible.

As I discuss in The Cell’s Design, flexibility is not the only feature of DNA that has been optimized. Other chemical and biochemical features appear to be carefully chosen to ensure its stability; again, a necessary property for a molecule that harbors the genetic information.

Optimized biochemical systems comprise evidence for biochemical intelligent design. Optimization of an engineered system doesn’t just happen—it results from engineers carefully developing their designs. It requires forethought, planning, and careful attention to detail. In the same way, the optimized features of DNA logically point to the work of a Divine engineer.

Resources
“DNA Soaks Up Sun’s Rays” by Fazale Rana (Article)
The Cell’s Design by Fazale Rana (Book)
“The Cell’s Design: The Proper Arrangement of Elements” by Fazale Rana (Podcast)

Endnotes

  1. Huiqing Zhou et al., “m1A and m1G Disrupt A-RNA Structure through the Intrinsic Instability of Hoogsteen Base Pairs,” Nature Structure and Molecular Biology, published electronically August 1, 2016, doi:10.1038/nsmb.3270.
  2. Duke University, “DNA’s Dynamic Nature Makes It Well-Suited to Serve as the Blueprint of Life,” Science News (blog), ScienceDaily, August 1, 2016, www.sciencedaily.com/releases/2016/08/160801113823.htm.
Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2016/08/17/dna-designed-for-flexibility