C. elegans: The Tiny worm giving us insight into the universe of Neural circuits

Author: Garrett Jones

C. elegans is a great model organism for neural processes for a couple reasons. C. elegans (in its hermaphroditic stage) has a total of 959 cells and will have no more than 959 cells. This is a great quality because as a scientist you have consistency among the organism being studied. Also, C. elegans has about 302 neurons and 8,000 synaptic connections. Now you might think this is a lot to focus on when studying the functions of neurons, but compared to the 80 – 100 billion neurons and 100 trillion synaptic connections in humans, C. elegans has a very small amount of neural circuitry. This is excellent because C. elegans exhibits the same 3 behaviors all organisms exhibit, so if these behaviors are related to neural circuitry it will be easier to observe a correlation between the two with fewer neurons to look at.

Even though C. elegans has a small neural circuit, it still has the same basic functions that the neural circuit has in any organism. These three functions are finding food (sensory), evading threats, and reproduction. Without these three vital functions organisms would die and its lineage would not be carried on. These functions can be traced to certain nerve cells and when obliterated by laser oblation the nerve cells cease to function. By doing this the function of specific nerve cells can be determined and mapped out.

Dr. Cornelia Bargmann identified that soil dwelling C. elegans can smell strong odors by ablating neurons until the organism could no long detect pungent odors. She identified a specific receptor molecule (odr-10) in a pair of olfactory neurons that can detect diacetyl, a chemical released from decaying food. C. elegans can use this diacetyl gradient released by decaying food to locate it for consumption.

While feeding, C. elegans either behave on their own, or in clumps/groups as foragers. The behavioral feeding is specific to each organism and is consistent for the duration of its life. Dr. Bargmann’s lab discovered that solitary foragers could be transformed into group foragers by inserting a gene (npr-1) into the organism’s genome. Npr-1 can be compared to neuropeptide Y in other animal systems. Neuropeptide Y regulates food consumption, mood, and anxiety. From this Dr. Bargmann concluded that the behavior could be altered by altering the genome of C. elegans.

Dr. Bargmann’s lab isolated a gene from C. elegans that effects the function of several neurons. This gene was later named nematocin because of its functional similarities to oxytocin and vasopressin. Normally C. elegans must complete behavioral steps to successfully mate. The steps are searching for a mate, contact, reverse turns, producing the vulva, insertion of the spicule, and transfer of sperm. Dr. Bergmann and her team realized that if C. elegans does not have the nematocin gene active all of the steps still occur. However, the steps do not occur at the correct time or order for fertilization to occur.

These are just a few examples of how the animal nervous system can translate sensory information into fundamental behaviors. This research is so important because it is linking biochemicals, neurons, and receptors in C. elegans to functional behaviors the organism has. If this can be linked in one organism it is possible that they can be linked in humans. If specific neuron functions, and receptor functions can be understood we can better understand the behavioral characteristics we have as humans.

 

References:

https://www.nature.com/news/neuroscience-as-the-worm-turns-1.12461 (link to article)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597094/

Memes from:

http://www.quickmeme.com/meme/3sq99t (laser meme)

https://memegenerator.net/instance/11259082/high-expectations-asian-father-u-working-with-c-elegans-in-lab-why-not-a-elegans (A. elegans)

Cancer Research: Where Everything We Think We Know Might be a Lie

Author: Mark Brien

New technology in cancer research has led to the discovery and desire to use non-invasive markers for cancer. Cancer markers are proteins or mutated genes that are used to pinpoint the cause of cancer. More often than not, these are discovered using discovery based research rather than having specific hypothesis and a predetermined experiment. This discovery based research looks for patterns in proteins and mutations to find the underlying cause without identifying the specific proteins.

The main problem with all of this is the experimental biases that result from it. A bias in an experiment is when the outcome is skewed, whether intentionally or not, based on the experimental groups. An example would be a test’s ability to screen for cancer with the two experimental groups being 70-year-old cancer patients and 25-year-old non-cancer patients. If the test relies on age as one of the markers, then a bias exists and would obviously prove successful in finding the cancer in the 70-year-old patients, or vice versa not finding it in the 25 year olds. This here is the problem with discovery based research techniques in trying to find patters to be used as markers without already having a specific marker in mind to search for.

The two main sources of bias in an experiment are the selection and randomization of participates before the trial begins, and how the equally the results of each group are assessed. Inequality in the baseline could stem from choosing participates based on whether or not it is already known that they have cancer or not. If scientists are trying to prove their test of identifying cancer markers correctly, they could have a bias of choosing only cancer patients rather than randomly selected individuals to prove the test successful.

On the other hand, if the results from each group are assessed in different ways. As stated earlier, biases could also be unintentional. If researchers are studying deaths from cancer, they might mistake death BY cancer for death WITH cancer due to not knowing a patient’s full treatment history. Just because a cancer patient dies, does not meant the cancer was 100% the cause of death so in some cases, “blinding” might be of good use to researcher.

This illustration shows how baselines may start out random but then the introduction of biases may lead to 2 distinct outcomes.

So how do we fix all this mess? The best way to minimize biases that occur in cancer research would be to implement strict randomness in baselines, as well as the blinded collection of data so that everything stays as true and non-skewed as possible.

References:

https://www.ncbi.nlm.nih.gov/pubmed/15685197

Memes from:

http://www.quickmeme.com

https://tenor.com

A Talk Is Not a Paper: How to Give a Good Talk

By Jonathan Omer

If you have ever had or will have to stand up and present ideas or data in front of an audience, then this blog is for you.

In my opinion, the vast majority of science talks are terrible. I don’t mean that the science is bad or that the speakers are not trying to present their work clearly. I mean that information is often presented in a muddled fashion, with distractions that prevent the audience from understanding the point and—all too often—the talks are simply boring. They are, therefore, a poor mechanism for communicating information to the audience. The result is that during most scientific meetings, one can observe that the majority of the audience has tuned out of many talks. They are checking their e-mail, surfing the web, or just staring blankly at the slides, not really absorbing the information. Often, these audience members blame themselves. They think they are not smart enough or sufficiently advanced in the field to understand the complex material presented in the talk. This represents a huge missed opportunity to communicate the excitement of science to a broad audience.

Let’s start, though, with an overview of the fundamental problems with most science talks.

First, most speakers manage to drain their talks of all of their enthusiasm for their work.

Second, most speakers rely on jargon and fail to communicate in plain language.

Third, most speakers employ their audio-visual aids in ways that make it hard for observers to understand the essential points.These are the most obvious problems with the vast majority of talks, but instead of harping on what not to do, let’s explore what can be done to prevent you from feeling bad.

The overall goal is to keep the audience intrigued and, dare I say, entertained.

First, you will keep or lose your audience in the first few minutes. Remember, they are on your side, at least at first. So, take their goodwill and run with it. Make it clear from the very beginning what the problem is and how cool you think it is. This may require backing up a bit from the specific topic of your paper. Not everyone is going to immediately think that studying the connections between quantum theory and chaos theory is the coolest project ever, so give them something to grab onto. In plain language, talk about the general nature of the problem. Use photos or illustrations or movies to orient your audience to the nature of the problem and the specific aspects you have studied. Don’t put words on these slides other than labels. Point to specific places in the illustration when you discuss this thing or that thing. Allow the audience to absorb the complexity of the images you are presenting and to accept your guided tour of the most important aspects for this presentation. Do not overwhelm them, but introduce them to the richness of the problem you have studied.

Now, start revealing your methods and experiments. This is the most important point where you must strike a balance between breadth and depth. You want to provide sufficient information to demonstrate that you have performed your work carefully and that your experiments are sensible, but you don’t want to drown your audience in details of your experimental methods. This will take some practice, but when you are using widely-used methodology you can usually assume that your audience will believe that you used appropriate methods with appropriate controls. They can read your paper for the details if they are interested.

It is often asked just how much detail should be provided in a talk. Younger speakers are often understandably nervous about not presenting their experiments in full, lest the audience think that they are not rigorous scientists. My advice is that you should be prepared to lose most of the audience on occasion as you dive into the details of an experiment, but then rapidly pivot back to a more general conclusion that can be understood by everyone. If you drag your talk into a swamp of details surrounding your experiments and you don’t return, then you can be assured that most people in the room will not follow you.If they aren’t as intelligent as you, they might think you are a great scientist. More likely, however, they will think the talk is boring. Of course, it is ideal if you can always use plain language, with minimal jargon, even when you are explaining your most sophisticated experiments. (Most talks are full of jargon so you must examine your language very carefully to minimize it.) The audience will not think you are dumb for using plain language. They will think you are brilliant for explaining such complicated work with such straightforward language. The ability to explain the most complex problem in the plainest of language is a sign of true understanding.

 

Reference Articles:

https://www.nature.com/articles/d41586-019-01041-9

https://www.nature.com/articles/d41586-018-07780-5

What NOT to Do (But I recommend watching for a good laugh):

Comedian Sam Hyde sneaks his way into a TEDx talk, and the results are hilarious
byu/rust_oxide invideos

Thinking Outside the Box: Emerging Model Organisms

Author: Hillary Acosta

For decades, cell biologists have studied the same genetic model systems that have answered the same limited questions. By turning our attention to the study of non-traditional model systems, scientist will be able to answer more diverse and interesting questions that were never able to be answered before. By choosing organisms based off of their biological attributes rather than their experimental history, scientist can expand their knowledge in the field of cell biology. This will lead to possibly some of the biggest scientific discoveries in cell biology.

Many of our most powerful tools can also be applied to these non-traditional model systems. Genomic sequencing and CRISPR-based technology are just a few examples of current tools that can still be used for these diverse model organisms.

Figure 1: Examples of emerging model organisms

Despite the exciting nature of non-traditional models, many of these non-traditional organisms have not been heavily studied. This will impose a few challenges on scientist.  One challenge is that new model organisms will need to be grown in a laboratory setting  to gain insight on their cell biology. Some of these model organisms will not fully adapt to a laboratory setting, therefore, a solution would be to start with a wide variety of species that may help to answer a particular research question, and then narrow it down to just a few. It will also be difficult to choose which techniques to try first and which questions to try to answer. A helpful tip to avoid getting overwhelmed would be to prioritize which  battles to fight first, and to leave some on the side for later.

In conclusion, emerging non-traditional model organisms will help scientist to find answers to questions that would be impossible to answer using traditional model organisms. With our knowledge of cell biology being able to expand, it will be exciting to see what the future holds for cell biology.

Read the full article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5077642/pdf/nihms813217.pdf

References for images:

http://nymag.com/intelligencer/2017/02/roll-safe-the-guy-tapping-head-meme-explained.html

Click to access nihms813217.pdf

https://memegenerator.net/instance/59804100/dwight-k-schrute-challenge-accepted

Is Graduate School an Option for You?

Author: Franki Carroll

As STEM majors slowly approaching the end of our undergraduate years, many of us have choices to make about our plans after graduation. Maybe you already have everything figured out, or perhaps you’re more like me and not really sure of anything.

At the end of my junior year, I knew I quickly needed to decide what my post graduation plans were going to be. When I started at Nicholls, I was a chemistry major with a pre-med concentration, so I’d obviously be going to medical school, right? Wrong. In the middle of my junior year I realized I wasn’t too sure if I wanted M.D. attached to my name, and it seemed like a waste of time and money to take the MCAT, apply to schools, and possibly attend a school for a year or two just to figure out if that was really the path I wanted to take in life. This lead me to look at why I thought I might want to be a doctor, and it turns out I was really more interested in research rather than patient care. This led me to looking into graduate school, and eventually applying and getting accepted into a program. Therefore, if you’re feeling a little lost and not sure about what you want to do after graduation, stick around and sit tight while I tell you all the reasons you should look into obtaining an M.S or even a Ph.D.

In my humble opinion, one of the biggest reasons to attend graduate school as a STEM major is that many programs will cover your tuition and they’ll pay you. That’s right, folks. Many graduate programs will pay you to join them. This stipend is usually around $30,000 a year, depending on the cost of living in the area the school is located in. Of course, you’ll be doing work in the form of research and being a teaching assistant; however, it’s fair considering graduate programs in other fields don’t pay their students or cover tuition.

Another reason to look into graduate school is the travel opportunities. After applying, many schools will pay for you to visit them to learn more about their program, meet professors, tour the campus, and explore the town you might possibly move to. Over the past month, a friend of mine has been to a different state every weekend touring different schools. Also, once you’re actually in graduate school and doing research, there are travel opportunities for conferences and for learning specialized skills. While touring graduate programs, I met a graduate student who spent a summer in Russia learning more about a certain spectroscopic technique.

This leads me to my final reason to look into graduate programs. Obtaining a higher degree allows you to exchange knowledge with some of the brightest minds in your chosen field. As a graduate student, and even after obtaining that higher degree, you will gaining a more in depth knowledge of something that truly interests you. Furthermore, you will be making discoveries that will add something of value to humanity. I believe that pursuing knowledge and research is a wonderful way to leave a mark on the world.

If you’re unsure of what path you want to walk down after you graduate from Nicholls, I highly encourage you to look into graduate school!

 

3-D Printing, Will it Change the Future of Medical Research?

Author: Logan Soulet

Recent antibiotics, medications, and vaccines created by drug researchers utilize various tests to determine their effectiveness of stopping certain diseases. Researchers have been developing treatments for illnesses such as bacterial infections, viruses, and cancer using in vitro methods to find biological processes that lead to the development of these sicknesses. The term “in vitro” means researchers must study their targeted disease in an environment outside of the diseased cells’ home. In the past, 2-D microenvironments created by researchers were used to sustain a sample of various diseased cells, such as cancer, in order to carry out the tasks necessary for experimentation. This technique has been successfully carried out for some time, however, with the introduction of 3-D printing and the exploration of its applications, researchers may have realized they can create better in vitro microenvironments using this technology.

Recent experiments implanted Hela cells, which are cancer cells often used in research due to their high survival rate, in samples of 2-D and 3-D microenvironments. The samples were allowed to grow for 8 days, then underwent a series of tests. It was found that cell samples in the 3-D culture multiplied 1.3-1.5 times as much compared to 2-D samples. After 8 days of growth, samples were taken, and two protein levels were analyzed from both the 3-D and 2-D samples. After analysis, it was determined protein expression was 2.3-2.5 times higher in the 3-D samples.

Lastly, drug resistance of both samples was tested at the end of the experiment. The results suggest that Hela cells in the 3-D microenvironment were more successful at maintaining their cellular shape and culture structure than the 2-D sample despite being affected by the drug (Zhao et al. 2014). Bringing this information together leads to the assumption that 3-D cultures would create healthier samples, therefore allowing researchers to more accurately observe the effects of drugs on cell cultures. Regarding the future of cancer research, scientists hope to use these more suitable 3-D microenvironments to create increasingly lifelike cultures to better understand cancers’ onset and its molecular secrets that keep us from curing this once and for all.

Check out the article: Three-Dimensional Printing of Hela Cells for Cervical Tumor Model in Vitro by Zhao et al. from Biofabrication
Figure 1: Stratton, Scott et al. “Polymeric 3D Printed Structures for Soft-Tissue Engineering.” Journal of applied polymer science vol. 135,24 (2017): 455569. doi:10.1002/app.45569
Figure 2: Zhao, Yu, et al. “Three-Dimensional Printing of Hela Cells for Cervical Tumor Model in Vitro.” Biofabrication, vol. 6, no. 3, 2014, p. 035001., doi:10.1088/1758-5082/6/3/035001.

How Might Environmental Estrogen Be Affecting You?

Author: Angelina Verhayden

Figure 1: Zebrafish- the model organism used in this study https://www.zebrafishfilm.org/

Environmental estrogens are endocrine disrupting chemicals that alter hormone signaling in humans as well as many other animals. One of the most studied ways it affects organisms is through the reproductive system. Environmental estrogens have been proven to decrease the quality and count of semen, increase the chances of breast or testicular cancer, and cause malformation of the urogenital tract. In more recent studies it has been found to alter the sexual habits of fish as well as cause feminization of males. Estrogen is known to be key in the nervous system, somatic cell growth, and the immune response. With all these known affects you must wonder how else these chemicals might be affecting your body.

All previous programs that screen for endocrine- disrupting activity only work for specific mechanisms and never for the whole of an organism. The transgenic zebrafish was chosen in this study to be the model used to tract tissue specific effects of estrogen. The transgenic zebrafish contained an estrogen promoter with estrogen responsive elements and green fluorescent protein(GFP) to cause a visible marker. From this study it was determined that environmental estrogen affects more than the reproductive tract after exposure. In the transgenic zebrafish estrogen was shown to affect the liver, forebrain, heart , skeletal muscle, neuromasts, otic vesicle/eye, and the otic vesicle/eye ganglions.

Figure 2: This image shows the fluorescence of GFP in the young zebrafish in response to environmental estrogen in specific tissues.

The study found that the different types of environmental estrogens will target specific tissues. This suggests that health effect outcomes will vary based on type of exposure. The study has given us a way to study the physical and pathological effects of environmental estrogens on organisms as well as insight into the tissues it affects.

Read the full article:  https://www.ncbi.nlm.nih.gov/pubmed/22510978

Engineered Zebrafish: A Way to Cure Diabetes?

Author: Keith Chenier

Type 1 Diabetes often results in people taking shots of insulin to maintain a healthy level of sugar in the blood stream. Diabetes is caused by reductions in B-cells in the pancreas. These B-cells produce and regulate the insulin that is released into the blood stream. A recent study used Zebrafish to perform the first whole organism screening to identify drugs capable of countering the effects of Type 1 Diabetes. They used high-throughput screening as the preferred technique; HTS is used to read the effects drug related  compounds have on living cells.

Zebrafish were an ideal model for the experiment because Zebrafish were being used in clinical trials at the time in studies related to leukemia patients; this made it an ideal model because the applications of this study will be used in medications for diabetes patients. Engineering their own Zebrafish for the experiment, they breed Zebrafish with a reporter gene that would allow them to have a marker when the gene got expressed. The expressed gene would fluoresce yellow if new B-cells were formed and red if pancreatic cells were stimulated by any drugs being tested. Another reason Zebrafish were used is because the larvae are transparent; this allowed them to view the fluorescence.

They discovered 24 possible drugs that could be used for treating diabetes; all triggered growth of B-cells or had the ability to make the endocrine system respond. Figure 1 shows a mixture of both the yellow and red fluorescence being active inside the pancreas. With the newly found 24 drugs, they will be able to move forward into clinical trial testing out medications for Type 1 Diabetes patients (Wang et al. 2015).

Figure 1: Zebrafish larvae showing both yellow & red inflorescence (Wang et al. 2015)

Link to article- elife-08261-v2

References

Wang, Guangliang, et al. “First Quantitative High-Throughput Screen in Zebrafish Identifies Novel Pathways for Increasing Pancreatic Beta-Cell Mass.” ELife, vol. 4

There’s a New Model in Town

By Christian Sells

For a long time, science has turned its spotlight on mice, who play a significant role in the biomedical world. Every person and their mama knows that. The use of mice as transgenic models for humans has contributed significantly to research and its findings. As popular as mice may be in the biomedical field, they still have their faults. It’s an imperfect model. Mice and primates may both be mammals, but their genetic and physiological characteristics are quite different, which can impede the extrapolation between research data and real-world, clinical data. In others words, the results won’t be too consistent. Bummer.

http://animalia-life.club/other/lab-mouse-cartoon.html

Thankfully, new research has led to the finding of another potential animal model for humans! The common marmoset (Callithrix jacchus), the cute New World primates, has been the center of attention of scientists as the newer and better model because of its small size, availability, and unique biological characteristics. Marmosets as a model would benefit many fields that fall under the biomedical research umbrella, such as neuroscience, stem cell research, pharmacology, immunity and autoimmune related diseases, and reproductive science. Due to the marmoset’s short gestation period, relatively short time to reach sexual maturity (12-18 months), and high offspring output (40-80 offspring in a female’s lifetime), they can potentially serve as practical models for transgenic techniques, which could greatly assists in the study of human diseases.

https://makeagif.com/gif/pigmy-marmoset-eating-tree-sap-9aysC6

Transgenic marmosets were produced using a lentiviral vector that carried an enhanced green fluorescent protein (EGFP) transgene. The lentivirus was injected in the perivitelline space of both naturally fertilized and in vitro fertilized marmoset embryos, and the embryos were then placed in surrogate mothers. Integration of the EGFP gene was then analyzed by using samples of tissues acquired from the infant marmosets, such as placenta, hair roots, skin, and peripheral blood cells. The EGFP gene was found to be successfully expressed in the analyzed tissues! Although, it was found to be expressed in tissues of certain subjects, but not in all of the selected tissues of all of the subjects. The expression of the EGFP gene in the tissues was assessed by examining EGFP fluorescence with fluorescent microscopy and immunohistochemical analysis. Germline transmission of the gene was also found to be successful by mating two of the second generation marmoset subjects that were found to have EGFP expression, which could allow for transgenic primate colonies to be made for research.

Figure 3: Five transgenic marmoset infants from the study that show EGFP gene expression (fluorescent green glow) in their paws

The use of marmosets as the new go-to animal model for human diseases could be crucial for new findings in biomedical research, and germline transmission found in the study serves as a huge finding for studying genetic diseases such as Huntington’s Disease. Hooray for science!

Read the article here: https://www.researchgate.net/publication/26249885_Generation_of_transgenic_non-human_primates_with_germline_transmission

 

 

Green Fluorescent Protein: The Molecular Spotlight

By: Ethan Guidry

With all the craze around bacteria and their molecular processes, it was time to upgrade the spotlights and shine better light on the world of molecular biology. These new and improved “spotlights” are known as Green Fluorescent Proteins (GFP) and help researches to keep an eye on their latest celebrity obsession of the cell.

GFP was first discovered in a species of jellyfish, Aequora victoria, and has now become one of the most important tools in molecular biology. The protein can be used in real-time analysis of gene expression, protein localization, and the inner workings of signaling-transduction pathways through protein-protein interactions. Researchers have found that once you tag a specific molecule with GFP within a cell, you can either:

1. measure the degree of fluorescence in the cell
2. measure the fluctuations of the fluorescent signal over time
3. measure the efficiency of the transfer of electrons involved in re-emitting light.

The degree of fluorescence in the cell is measured in processes like gene transcription through a technique called fluorescence-activated cell sorters (FACS). This technique works by tagging desired parts of the cell with GPS and analyzing the light they deflect as they pass through a laser. If transcription becomes up-regulated, then more instances of fluorescence should be seen in the desired part of the cell. This allows researchers to measure the rates of transcription and the degree of gene expression.

Figure 1. Diagram of a fluorescence-activated cell sorters (FACS)

Fluorescence correlation spectroscopy (FCS) is a technique used to measure the degree of fluctuation in fluorescence over time. The intensity of fluorescence is affected by the Brownian motion (random movement of particles through collisions) and analysis of this intensity gives the average number of particles and average diffusion time. Eventually, the concentration and size of the desired molecule can be determined from this data. This tool allows us to monitor the location in which cellular processes take place, the movement of cell parts, and to identify and analyze the physical features of new and existing cell parts.

Figure 2. The various movement of particles, their concentration, and a fixed graph of Fluorescence correlation spectroscopy (FCS) .

Fluorescence resonance energy transfer (FERT) is a technique used to measure the efficiency of the transfer of electrons involved in re-emitting light. If the concentration of FERT is low, then the distance between the fluorophores (fluorescent chemical compound that can re-emit light on excitation) is large. If the concentration of FERT is high, then the distance between fluorophores is small. This data allows researchers to analyze protein-protein interactions and signaling cascades in real time.

Figure 3. The correlation between concentration of fluorescence resonance energy transfer (FERT) and distance between fluorophores.

Although GFP has quickly become a gold standard tool in molecular biology, it is not without its limitations. GFP is hard to detect at low expression levels and its use dependent on oxygen availability and pH levels. There are also concerns regarding the sensitivity of GFP due to its folding rate and stability in bacterial cells. Despite the limitations, GFP is an exciting, new tool that will only continue to better shine a light on the complexity of molecular biology.

Read the full article:

https://www.ncbi.nlm.nih.gov/pubmed/12207688