Author: Prashant Bhat

“Synthetics” – Berkeley Scientific’s Spring 2014 Issue

BSJ Synthetics

Berkeley Scientific publishes undergraduate research, features articles, and interviews with UC Berkeley professors spanning many areas of science. In the Spring 2014 issue of Berkeley Scientific Journal, we explore how recent technological and biomedical developments have advanced our understanding of “synthetics” in science. We are constantly surrounded by synthetic science— manmade technological advancements that enable us to communicate faster, manipulate genes, and progress toward cleaner energy. UC Berkeley professors and other members of the academic community are currently researching cancer immunotherapy, genome editing, and solar energy among other topics. These accomplishments among many others have garnered global attention. Now is the perfect time to dedicate the current BSJ issue to “synthetics.”

Lab-on-a-chip

This semester’s issue is filled with high quality research, features articles, and an interview with an award-winning Cal professor. For an understanding on how synthetic science works on a microscopic level, read our feature articles about DNA as building blocks of nanotechnology, magnetoelectric materials, and “lab on a chip.” Departing from micro-scale technology, explore interesting articles on “Manufactured Memories,” artificial heart devices, and “Bright Ideas in Solar Energy.” Additionally, Berkeley Scientific had the opportunity to interview Jan Rabaey, a professor of Electrical Engineering and Computer Science about his research on neural prosthetics and their future applications. I invite you to read the second issue of Berkeley Scientific Journal’s eighteenth volume, filled with fine articles and undergraduate research papers on the topic of synthetics.

 

Prashant is a senior undergraduate student studying biochemistry and molecular biology at the University of California, Berkeley. He currently is Editor-in-Chief of Berkeley Scientific Journal, where he became interested in science journalism and its propensity to motivate general audiences.  Read the current issue here. Follow BSJ on Twitter.

 

Category: Artificial Intelligence, Bacteria, Clinical Trials, ethics, Interviews, Medicine, Memory, Neuroscience, PLoS, PLoS Biology, PLoS Blogs, PLoS Medicine, ResearchBlogging, Science Journalism, Students, The Student Blog | Tagged , , , , , , , , | 1 Comment

Genome editing just got a lot easier

This post is cross-posted with Berkeley Scientific Journal

If you’ve recently taken a glimpse at the front page of any major science news outlet, it is likely you are no stranger to an emerging genome editing technology known as CRISPR/Cas9. With the help of RNA, Cas9 (a bacterial enzyme) can be programmed to target specific locations within the human genome, enabling scientists to delete, modify, or insert sequences that may treat, or even cure patients with genetic diseases. Although the CRISPR/Cas9 field is still in its early stages, major breakthroughs have been made recently, paving the road for a new line of gene therapy.

Just a couple weeks ago, researchers at Nanjing Medical University and Yunnan Key Laboratory reported successful usage of Cas9 in monkeys, thereby progressing toward the exciting possibility of editing human genomes. They injected Cas9 into monkey embryos and impregnated female monkeys with the resulting eggs; quite

These set of twins were born with targeted deletions in their DNA as a result of Cas9.

These set of twins were treated with Cas9 as embryos and as a result, born with targeted deletions in their DNA.

remarkably, the newly born monkeys had deletions in the targeted gene of interest. In the world of science, where expected results sometimes never come to fruition, this marks an important stepping-stone in Cas9 technology. Targeting genes with this high degree of specificity could potentially lead to therapies that will prevent individuals from developing genetic diseases.

Cas9 looks for PAM sequences (gold) and matching sequences before cutting the DNA (picture by KC Roeyer)

Cas9 searches for PAM sequences (gold) and matching sequences before cutting the DNA (picture by KC Roeyer)

In the same week, a paper published in Nature revealed the mechanism by which Cas9 finds target DNA sequences tens of base-pairs in size within a genome that contains three billion base pairs. Interestingly, the researchers showed that Cas9 searches for a specific sequence known as the PAM – if the target doesn’t carry this short DNA tag, the sequence is neither recognized nor cut. Samuel Sternberg, lead author on the paper, explains that the presence of PAM sequences “accelerates the rate at which the target can be located, and minimizes the time spent interrogating non-target DNA sites.”

One of the most recent discoveries came out last week in Science magazine: two structural biologists at UC Berkeley, Jennifer Doudna and Eva Nogales, published the structure of Cas9 from two different organisms, providing key insights into the mode of DNA recognition and cleavage by the RNA-guided enzyme. Fuguo Jiang, one of the lead authors on the paper, said, “although the two Cas9s are from different organisms, and overall they look very different, when you superimpose the two structures, their functional domains are very similar. This suggests all the Cas9s have a similar mechanism to make cuts in DNA.” Additionally, the paper revealed an important loop within Cas9 is responsible for recognizing the PAM. As for what this means for the future of CRISPR/Cas9 technology, Jiang elaborated, “The original Cas9 recognizes one particular PAM, but if you can engineer it to recognize a different PAM sequence through mutagenesis, that would be great. The genome sequence is usually fixed. But what you could do is change the PAM sequences that Cas9 recognizes and tailor it to target more genomic loci. In this way, we can expand our Cas9-based genome-editing toolbox.” This discovery, along with the physical mechanism by which Cas9 locates target sequences, may help improve the efficiency of targeted gene editing.

And that’s not all. Editas Medicine, a new company co-founded by some of the leading scientists studying Cas9 aim to translate its genome engineering technology into a novel class of human therapeutics. These therapies are destined to make significant medical advances for people with genetic diseases including, but not limited to, Huntington’s disease, cystic fibrosis, and Alzheimer’s. Since modern sequencing technology has produced a massive amount of human genome sequences, mapping diseases to certain genomic coordinates is becoming faster and easier. With this valuable sequence information, the CRISPR/Cas9 system can simply be engineered to make positive changes in specific diseased DNA sequences and restore normal function.

Editas Medicine's goal is to further develop CRISPR/Cas9 technology into a novel class of human therapeutics. Pictured from left: Jennifer Doudna, Feng Zhang, Keith Joung, and David Liu

Editas Medicine’s goal is to further develop CRISPR/Cas9 technology into a novel class of human therapeutics. Pictured from left: Jennifer Doudna, Feng Zhang, Keith Joung, and David Liu

Genome engineering earned researchers a Nobel Prize in 2007, but with Cas9 speeding ahead, I wouldn’t be surprised if one is awarded to a Cas9-er in the near future.

 

**While writing this article, a paper was published in Cell that reveals another structure of Cas9, but now bound to its target DNA. This structure provides more information about the molecular mechanisms by which Cas9 cuts its targets and will further aid researchers in improving genome-editing tools**

If you want to learn more about how Cas9 functions, check out this video produced by a student in Eric Greene’s lab at Columbia University:

Cas9: The Enzyme, The RNA, & The Virus

Cas9: The Enzyme, The RNA, & The Virus (video by Myles Marshall)

Cas9: The Enzyme, The RNA, & The Virus (video by Myles Marshell)

 

 

 

 

 

 

 

 

 

photo (1)Prashant is a senior undergraduate student studying biochemistry and molecular biology at the University of California, Berkeley. He currently is Editor-in-Chief of Berkeley Scientific Journal, where he became interested in science journalism and its propensity to motivate general audiences.  Read the current issue here. Follow BSJ on Twitter.

Category: Bacteria, Cancer, Genetics, News, PLoS, PLoS Biology, PLoS Blogs, PLoS Genetics, PLoS Medicine, PLoS Medicine Week by Week, PLoS Medicine's Daily Click, ResearchBlogging, Science, science journalism, The Student Blog | Tagged , , , , , , , , , , , , , , | 10 Comments

Science of Stress – Berkeley Scientific Journal’s Fall 2013 Issue

This post is cross-posted with Berkeley Scientific Journal

Twice each year, Berkeley Scientific publishes undergraduate research, interviews with distinguished Cal faculty, and feature articles spanning diverse scientific disciplines.

If you are a student and are in the midst of studying for final exams, stress is not an uncommon feeling. In this semester’s issue, we chose to explore stress in different realms of scientific thought. How does one clearly define stress? In the human body, stress takes on the form of various chemicals and stress-inducing hormones, thereby altering the body’s physiology. In the current issue, Preethi Kandhalu explores the biological mechanisms of stress and Jenna Koopman provides a cautionary description on the dangers stress can have on fertility. Integrative Biology Professors Michael Shapira and George Bentley talk about their research and how it pertains to biological mechanisms of stress.

However, stress is not limited to the biological systems. Engineers depend heavily on creating safe structures in which extreme levels of physical stress are applied.

Structural failures result in perilous consequences, as witnessed by the devastating building collapse in Savar, Bangladesh earlier this year. Aditya Limaye sheds light on the current technology surrounding carbon nanotubes and its properties that make it a suitable candidate for 21st century infrastructure. Tensile strength is not limited to large physical objects, however— read Alex Power’s entertaining article on how spider silk is perhaps strong enough to withstand an oncoming train.

With new scientific information filling new textbooks annually, how do we decide what particular ideas to stress? On a more philosophical level, Jahlela Hasle writes about the “language of science” and its inevitable evolution over the years. We invite you to join us in exploring the many ways in which stress factors in our lives, from the social to the biological, to the mechanical, to the linguistic.

 

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Prashant is a senior undergraduate student studying biochemistry and molecular biology at the University of California, Berkeley. He currently is Editor-in-Chief of Berkeley Scientific Journal, where he became interested in science journalism and its propensity to motivate general audiences.  Read the current issue here. Follow BSJ on Twitter.

Category: Stress, The Student Blog | Tagged , , , , , | 2 Comments

RNA-Based Therapies Meet the 21st Century

This post is cross-posted with Berkeley Scientific Journal 

Thousands of medications exist to counteract effects of various proteins and enzymes.

Thousands of medications exist to counteract effects of various proteins and enzymes.

We have all taken aspirin for minor aches, known someone who takes simvastatin to control elevated cholesterol, or are related to someone with hypertension who is prescribed ACE inhibitors for treatment. Most medications and over-the-counter drugs like these target enzymes (specialized proteins) that are directly involved in producing effects such as pain and elevated cholesterol levels.

Targeting RNA

Although most medications rely on targeting appropriate enzymes for specific treatment, a new class of therapy is advancing rapidly from the bench to the bedside. These are RNA-based drugs such as antisense therapy that target an earlier step that prevents the disease-propagating protein or enzyme from being produced in the first place. But what type of diseases can these RNA-based drugs target? It would be detrimental to a cell if a particular enzyme was not produced at all- just imagine how long you would last if you stopped producing the enzyme responsible for making cholesterol (not very long). Even though cholesterol gets a bad rep for its role in heart disease, it plays a critical role in hormone synthesis and the maintenance of cell membranes. However, when the expression (scientist-speak for ‘production of protein’) of a disease-causing protein is highly controlled, it could have great therapeutic value.

The central dogma.

The central dogma. DNA is the hereditary material, RNA relays that information to make protein.

The Central Dogma: Revisited

The central dogma of molecular biology is that DNA makes messenger RNA (mRNA), which in turn makes protein. We all know DNA to be the genetic data storage center of our cell, and mRNA as the intermediate “delivery guy” that relays its information to make protein. Our cells naturally produce another type of RNA called microRNA (miRNA), a newly found class of non-coding small RNAs that regulate expression of mRNAs by physical contact and prevent the mRNA from being translated into a protein. Currently, most pharmaceutical drugs interact with the last step in this process; however, inhibiting microRNA function by an anti-microRNA (anti-miR) drug can effectively control the production of specific enzymes involved in a disease process.

Antisense drugs target mRNA, whereas traditional drugs target protein.

For example, if a particular cancer results from the under-expression of a certain enzyme, a specific anti-miR drug could be developed to inhibit the miRNA that regulates the mRNA corresponding to that enzyme, resulting in increased enzyme production.

 

21st Century Approach to Medicine

Companies such as Isis PhamaceuticalsRegulus Therapeutics and Alnylam Pharmaceuticals are dedicated to creating RNA-based therapeutics for a wide range of diseases including hypercholesterolemia (high cholesterol), hepatitis C, glioblastoma (brain tumors), kidney fibrosis, and atherosclerosis. In recent years, antisense drugs have made it to the clinic and been approved by the FDA to begin treatment of patients.

Early this year, the FDA approved mipomersen, an antisense drug produced by Isis Pharmaceuticals that targets the mRNA responsible for making apolipoprotein B. The medication has been lauded by families with familial hypercholesterolemia, a genetic disorder responsible for producing unusually high levels of low-density lipoprotein (LDL) cholesterol (commonly referred to as “bad cholesterol”).

In addition, RNA therapeutic technologies have the potential to treat diseases that are globally prevalent. For example, according to the CDC, more than 170 million people are chronically infected with Hepatitis C Virus (HCV) worldwide. Current treatment for HCV requires a combination of peginterferon and ribavirin, which eliminates the virus from over 50% of infected individuals. Administration of these drugs cause major flu-like side effects, making them difficult to take. Additionally, the fact that their efficiency is not very high and that they need to be taken twice daily in some cases calls for alternative treatment options.

For chronic cases, the face of HCV treatment may change with novel antisense/anti-miR drugs that target the RNAs that help replicate hepatitis virus. By targeting an earlier stage in the pathway, these drugs may be more effective in eliminating the virus from replicating on a shorter time scale. A couple anti-miR drugs are being developed and are in clinical and preclinical stages. Santaris Pharma, based in Copenhagen, Denmark has miravirsen in phase 2 clinical trials and more recently, Regulus Therapeutics in La Jolla, CA nominated a clinical candidate, RG-101, for the treatment of HCV. Both of these drugs are aimed at targeting miR-122, the microRNA in the liver that HCV hijacks and allows it to self-replicate. The drugs are still in very early stages, but with other antisense and RNAi drugs gaining fame for their effectiveness against chronic diseases, the development of RNA-based therapies is definitely worth following.

 

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Prashant is a senior undergraduate student studying biochemistry and molecular biology at the University of California, Berkeley. He currently is Editor-in-Chief of Berkeley Scientific Journal, where he became interested in science journalism and its propensity to motivate general audiences.  Read the current issue here. Follow BSJ on Twitter.

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Stunning Critters, Silent Killers

Science students (like me) and research scientists are often attracted to the aesthetic beauty of the physical and natural sciences at both the microscopic and the macroscopic level. Oscar Wilde quite vividly noted, “Life imitates art far more than art imitates life.” While many art critics may raise eyebrows to the notion that microorganisms form a distinct genre of art, us scientists rebut (per usual) with this artistic rendition of San Diego beaches using differently fluorescing bacteria:

Tsien

Agar Plate of Fluorescent Bacteria Colonies (Roger Tsien lab, UCSD)

But “life imitating art” is not restricted to recombinantly engineered bacteria that fluoresce different colors.  Other forms of microscopic life are just as beautiful, albeit much more mysterious and catastrophic than the harmless “garden-variety” bacteria that scientists use for everyday experiments. It is usually the mysterious and the life-threatening natural phenomena (i.e. tsunamis, tornados, violent thunderstorms) that pique people’s consciences. Many find an eerie beauty within episodes of these catastrophic events—hundreds of storm-chasers literally run into the belly of the beast when they purposefully follow life-threatening storms. Some chasers seek a thrilling adventure, and many others are just enchanted by the beauty of horrific phenomena.

Horrific phenomena find a way into the biological world through the breathtaking phenomenon commonly known as “red tide,” an event caused by special species of algae. Most people who have heard of red tides usually have the misconception that these algal blooms always have devastating consequences. But not all red tides are harmful, which consequently has resulted in scientists distinguishing red tides (which may or may not be toxic to aquatic life) from harmful algal blooms, or HABs (which are undeniably harmful, but may or may not be colorful).

A visually spectacular algal bloom occurred in San Diego last year in November.

A visually spectacular algal bloom occurred last November in San Diego, CA.

Cape Cod, 1987. Dead humpback whales washed ashore after ingesting fish laced with toxic algae (Photo by G. Early)

Cape Cod, 1987. Dead humpback whales washed ashore after ingesting fish laced with toxic algae (Photo by G. Early)

While most algae are not harmful, a small percentage of these microorganisms do pose significant environmental and health concerns to coastal communities. There are two main ways in which these rare algal species are particularly harmful.

Saxitoxin Toxicity

The first method directly kills aquatic life through toxic buildup. What causes these rapid algal blooms? A bloom occurs when a single-celled algae rapidly divides by simple asexual reproduction when nutrient resources are abundant. Although it is not entirely clear what exactly triggers these events, the consequences are well known. Harmful algal blooms are notorious for killing tens of thousands of marine animals that ingest the potent algae synthesized neurotoxin, saxitoxin (STX). Cases have been reported off the coast of Cape Cod, where the algal bloom of the species Alexandrium fundyense caused a mass death of a dozen humpback whales that accumulated lethal doses of saxitoxin. Just last week, tens of thousands of fish died due to a HAB along the Clifton shore in Karachi, Pakistan.

Saxitoxin causes paralysis, and even death if exposed to high enough quantities. Saxitoxin acts by blocking sodium channels in nerve cells. Sodium and potassium channels are essential for normal neuronal function—i.e. they help relay important sensory information to the brain. If sodium channels are blocked, nerve cells are unable to fire, eventually resulting in paralysis or death. Although saxitoxin is extremely toxic, affected dead fish do not accumulate high enough levels of toxins to have a lethal effect on humans who eat seafood. However, the potent toxin has made its way onto the United States military’s list of chemical weapons, which poses ethical questions about its potential misuse.

Eutrophication: Oxygen Depletion

The second way in which algae populations can threaten life is indirectly through the eutrophication of bodies of water. Lazy pet goldfish owners likely may have witnessed this unfortunate event. When algae build up rapidly in a body of water (such as a fish tank) due to the high availability of nutrients such as phosphorus, the algae deplete the oxygen supply for fish and other aquatic organisms. Over time, if the algae is not cleaned or eaten by other species, the fish suffocate and die due to a lack of oxygen. This unfortunate eutrophication event happened a few years ago to the beautiful Batiquitos Lagoon­ in my very own hometown of Carlsbad, CA (don’t worry, this story has a happy ending. The City of Carlsbad worked hard to fix the issue).

Eutrophication of a lake. Algae densely builds up on the surface, depleting oxygen levels below the surface of the water.

Eutrophication of a lake. Algae densely builds up on the surface, which depletes oxygen levels below the surface of the water. This results in death of aquatic life that depend on oxygen for gas exchange.

At the same time, algae can be a double-edged sword. It is important to note that most microscopic life—including many types of algae—is not hazardous, but rather a vital component of the ocean food network, in which they act as a source of food for fish and other aquatic animals. In fact, to make sure I don’t belittle the importance of algae, some scientists propound that over 80% of the earth’s atmosphere can be attributed to the photosynthetic blue-green algae (AKA cyanobacteria).

A nontoxic algal bloom off the coast of New Zealand. (Photo by M. Godfrey)

A nontoxic algal bloom off the coast of New Zealand. (Photo by M. Godfrey)

Nevertheless, harmful algal blooms continue to occur sporadically. While visually spectacular, they threaten aquatic as well as land ecosystems. Not only do these episodes wreak biological damage, they have costly economic consequences as well. For example, it is estimated by the Woods Hole Oceanographic Institution that the potential magnitude of economic losses due to harmful algal blooms in Australia alone are close to $200 million in US dollars annually. This is truly devastating for fisheries that suffer a bad rep once customers lack confidence in the quality of fish.

As of now, there really isn’t much we can do to prevent harmful algal blooms, but governments are now accustomed to quickly take action if there were ever to be one in the near future. When that visually spectacular phenomenon does occur, make sure to witness the natural enigma and thank the microscopic world for its special contribution to a uniquely natural art form.

 


photo (1)Prashant is a senior undergraduate student studying biochemistry and molecular biology at the University of California, Berkeley. He currently is Editor-in-Chief of 
Berkeley Scientific Journal, where he became interested in science journalism and its propensity to motivate general audiences. Follow BSJ on Twitter.

 

Category: Art, Bacteria, Environment, The Student Blog | 2 Comments