Author Archives: John Modarres

All good things must come to an end

This summer was fulfilling in all the ways I had hoped. I got the chance to meet great people in both BSURF and my lab. I am so glad I was a part of this amazing opportunity and I am saddened that it is over. My career choice was influenced in a positive direction toward research. I realize the potential for knowledge that a career in research can provide. The intrinsic value of discovering something new is something I never realized until I myself was published in a research paper on amitifadine. To keep it simple, research is a lot more interesting than I had realized. While I am not quite certain on my career path right now, I can say without a doubt that a career in research isn’t off the table.

My ideas of science have changed in a positive way as well. I now can see what properly using the scientific method can discover. In high school all the labs I did had a right and a wrong conclusion. This is the first time in my life where there is no right answer as my lab is the first in the world to discover what it did. The experience of working with live rats is one that I thought I would only have the chance to do years after graduation. The fact that I am able to put this on my resume is one that I do not take for granted.

I would like to thank my P.I Dr. Edward Levin for giving me the opportunity to work in his lab. It was a great experience and I definitely plan on coming back sometime in the future. I would also like to thank Dr. Grunwald for allowing me to be a part of this program (especially since he still let me, I passed the deadline).

Unfortunately, all good things must come to an end and I look toward my future at Duke in a brighter light than before BSURF.

See you in a month everyone!

You are what you eat

The most fascinating talk in my opinion was Dr. Lawrence David’s talk about gut bacteria. What most people don’t realize is that their gut bacteria play a gigantic role in many aspects of their wellbeing. From energy levels to mood to thinking capacity, one’s gut microbiome plays a crucial role.

Dr. David explained how the food you eat has a direct effect on your gut microbiome meaning that your microbiome can change corresponding with a change in diet. This would make sense when you think about why those who eat healthy foods feel better than those who don’t. People who eat good have good gut bacteria which effects all other aspects of their biology. The only turnoff was how he conducted the study, he literally sampled stool from people. To quote the great Jeff Goldblum, “Your scientists were so preoccupied with whether or not they could, they didn’t stop to think if they should”. While this made me question the point of the research, Dr. David did a great job with explaining the importance of the research and why it was necessary. His career path was especially interesting seeing as though he was able to eat street food for one whole year as part of his research. The work he does by giving people foods and testing their subsequent stool is interesting and gross at the same thing.  What shocked me was the fact that while he was in his 30’s, he like he was 22. It just goes to show the importance of a good diet on aging.

Amitifadine, a Triple Re-uptake Inhibitor, Reduces Self-administration of the Opiate Remifentanil in Rats: Abstract

Drug addiction is do to neural systems that may be altered by different drugs. Similar drugs that can affect nicotine self admin can also affect opioid self-administration. One such drug is amitifadine. We have found a correlation between reduced remifentanil use both acute and chronic when being treated with amitifadine doses of 5, 10 and 20 mg/kg. Repeated treatment with 10 mg/kg of amitifadine reduced remifentanil self-administration chronically, even after cessation of treatment. There was no significant affect on feed motivated responding when being treated with the 10 mg/kg amitifadine dose. Amitifadine extended and maintained anti-nociceptive effects while not attenuating remifentanil-induced analgesia. These studies with amitifadine show promise as the drug can be used to reduce opioid self-administration in patients while not negating the pain killing properties that make opioids so desirable. Further studies are needed to determine the efficiency of amitifadine as a drug that combats opioid addiction.

 

 

(Levin, et al. 2019)

If one more rat poops on me I swear to God…

A day in the lab is what you make of it. The quicker you are, the sooner you are finished with work. In my lab, it seems as though there is a hundred different studies being done at once. I have only one study I work on and it’s my job to complete it to the best of my abilities.

As soon as a arrive at the lab, I immediately get started. My working partner Graham will tell me what ha has already done and what I need to do. Without hesitation I get to work knowing that the more time efficient I am, the quicker we are done (something Graham is constantly reminding me of). I usually start with flushing the chambers and getting them ready by installing the syringe of Remifentanil. The dose of Remifentanil is based on the weight of the rat; therefore, we must weigh and prepare the rats before this step takes place. Weighing the rats is difficult as they wont stop moving. This makes it hard for the scale to get an accurate measurement. Once this is done the rat’s catheter is flushed to make sure blood clots are removed before the Remifentanil self-administration trial begins. A sheet is provided to see which rats get injections and with what they will be injected with. The trial cannot start until these rats have their injections making this step critical in terms of time efficiency. Graham has noticed that I have become very good at this and thus I am in charge of injections most of the time. Older rats are the best because they take the injections like a champ. The younger rats however seem to freak out and do their best to poop on you as much as possible. It is hard to treat an animal with respect when it does this but of course you have to. Once the rats are in the chamber, we start their trial via a computer. During the hour we wait, I usually feed the other rats while Graham cleans old cages. An hour later we must take all the rats out of the cage and flush them to prevent catheter clogging overnight. While I am flushing the rats, Graham is flushing the chambers and imputing data. We then put the rats away and make sure all the drugs are properly stored. We then get things on order for the next day and then head home.

They say a diamond is a girl’s best friend because it lasts forever. You know what else lasts forever? Plastic

As we continue to degrade our planet, we must find new ways to save the environment. Realistically stopping all carbon emissions will be impossible in the next few years and thus is not an option. Instead geoengineering might be the only way to save the planet from climate change. In a similar way the problem of plastic in our oceans must be addressed in this “outside the box” manner as well. While manually cleaning up our oceans is impossible considering the scale, alternatives must be considered. One of those alternatives is plastic degrading enzymes as discussed in Ella’s presentation.

Ella is working with Dr. Jason Somarelli on a genetically altered enzyme that can breakdown plastic. By using error prone PCR, she hopes to find a strain of bacteria that can breakdown plastic using a form of artificial selection of bacteria. A library of different bacterial strains will be made and will be used in testing. If such a strain could be found, billions of pounds of plastic could be degraded helping the fragile marine ecosystem avoid collapse. What surprised me from the presentation was not that by 2050 more plastic will be in the ocean than fish biomass, rather the fact that plastic doesn’t already outweigh marine fish is truly shocking. Saving the oceans is critical for the world not only because it’s the right thing to do. The ocean provides trillions of dollars in economic growth when considering tourism and the wild caught seafood market. Billions of people rely on the ocean for protein and its destruction would be the downfall of millions of people. Somali pirates only exist because the fishing industry in Somalia collapsed do to over-fishing and pollution. Since the fisherman in Somalia could no longer fish, they turned to piracy. Just imagine what would happen if this occurred worldwide.

One concern I do have is what if these plastics escape into society? imagine a world where bacteria is spreading that can destroy plastic. Society would crumble if plastic started to decay. industry and infrastructure would be destroyed leading to our downfall. Scientists for years have tried to fix problems with solutions that make things worse. Blue Tilapia is a fish native to Africa that was introduced in Florida to control algae. That backfired and now the species is causing environmental degradation. Due to erosion caused by bad farming practices, Kudzu was introduced to stop soil erosion. This plant later would spread like the weed it is causing massive forest loss due to its ability to choke out trees. When altering the environment, the consequences are often worse than the original problem. So while degrading plastic seems like a great thing, proceed with great caution.

 

The Career of Dr. Edward Levin

Dr. Levin is Chief of the Neurobehavioral Research Lab in the Psychiatry Department of Duke University Medical Center. He works as both a professor and a researcher in the Department of Psychiatry and Behavioral Sciences. He is currently in charge of a multitude of investigations centered around addiction and neurobehavioral toxicology. His research has led to many discoveries centered around the effects of substances of the brain and how this chronically effects an organism’s biology.

Dr. Levin started off his career as a student at Penn State University where he was initially premed. Due to his interest in the mind, he switched his major to psychology and later transferred to University of Rochester. He attended the University of Wisconsin for grad school and earned a master’s in psychology. He later earned a PhD in environmental toxicology. He later taught toxicology seminars, an experience he said was OK but was a lot of work.

Throughout his career, he discovered many different things related to behavior and toxicology. One of the first things he researched was link to cognitive impairments with exposure to electrical transformers. He also studied chlorine in water and how its reaction with organic materials creates trichloromethane otherwise known as chloroform which is carcinogenic. He told me that while drinking chlorinated water does slightly increase cancer rates, it significantly reduces infectious diseases and thus should be added to the water supply. Later in his career he started to study drug abuse primarily. Nicotine was the drug he studied heavily in his career due to its widespread use across the globe and its addictive properties. He found that it has cognitive enhancing abilities including how it may lessen the onslaught of Alzheimer’s disease. Haloperidol is another drug whose side effects he is credited for studying. He determined that tardive dyskinesia is a side effect of Haloperidol.

Dr. Levin’s primary focus at the moment however is opioid abuse. He is currently focusing on treatments for addiction by administering drugs. One of such studies I am currently working on. He is currently studying a drug that blocks the re-uptake of certain neurotransmitters. This acts as an indirect agonist to the opioid drug. His research found that the drug currently being studied as a treatment for opioid abuse has been shown to significantly reduce nicotine self-administration. When studying opioid abuse, the drug being used as the opioid is Remifentanil due to it’s rapidly acting properties as well as it’s very short half-life. He hopes that by finding a drug that treats addiction, the deaths from opioid overdose in this country may decrease.

When asked why he enjoys science, Dr. Levin credited the joy of discovery and how it is a tremendous reward. He said it is an incredible feeling when, through your research you are the first person in the world to know something. As for what he would change, the first thing that came to his mind was bureaucracy. He fills out too many forms and wrights too many proposals for funding. Then again, what other industry lacks excessive bureaucracy?

Using drugs to stop the prescription opioid crisis.

As everyone by now has heard, the U.S is experiencing an epidemic. I’m not talking about infrastructure or climate change or income inequality, rather I am referring to the current opioid crisis. You see, a couple of decades ago big pharma companies created drugs that resemble the effects of opium, a drug known for its pain killing effects as well as its capability to start wars. These drugs where marketed as same pain killers that where much more effective then aspirin or ibuprofen. Soon, doctors were prescribing these pills left and right to people with chronic pain, post-surgery pain, or even people with bad tooth aches. Eventually however people got hooked. You see, drugs that are very similar in molecular structure to heroin started getting people addicted. Who would’ve guessed that? People started to take more of these drugs to get their “fix” and this only increased their tolerance. Many of these people would turn to stronger opioids like heroine or fentanyl. These drugs have a high likelihood of overdose with chronic use. It is no surprise then that overdose has surpassed car accidents as the leading cause of death in the U.S.

What can be done about this tragedy? While many have suggested tighter regulations on big pharma, who are we kidding by expecting these regulations to become law? Instead, the best alternative is to try to stop people from wanting the drugs in the first place. In my lab I have been assigned to test different drugs on rats to see if it stops the cravings for opioids. By using the classic Skinner Box, rats are trained to self-administer Remifentanil, a type of opioid, in a manner that mimics addiction. Whenever the rat presses the correct lever, a dose of Remifentanil is intravenously injected into the rat via a catheter. Once these rats are dependent like a human addict, we will give them either the test drug (we are testing different drugs in different individual studies) or saline (as the control group). If it is found that rats injected with the test drug stop self-administering Remifentanil, it would mean that this drug could potentially be prescribed to opioid addicts as a way to curb their addiction. If successful, the drugs we are testing could save countless lives from potential overdose.

The use of drugs to treat behavioral traits is not knew. Instead of therapy or lifestyle changes, many people with anxiety or depression will opt to take SSRI’s to treat their mental illness. This has proved to be more practical, and often more effective than therapy and has greatly helped millions of people. While all mind-altering drugs have potential side-effects, the illness or addiction is often worse than the occasional dizziness or mood swings. While it may seem ironic, the truth of the matter is that our only hope to fight drug use is using more drugs. Welcome to the 21st century everyone!

What to expect from this experience.

This summer I was given the opportunity to work in Dr. Levin’s lab and gain valuable experience that I will use to further my goals of studying biology. My expectations for this opportunity are geared towards knowledge rather than anything else. I expect to gain knowledge regarding not only how to conduct myself in a lab, but also how biological related research works.

The innermost working mechanisms of a lab are, as I expected to be the case, very extensive and precise. To simply research the effects of Remifentanil on rat addiction requires a great deal of bureaucratic hoops such as drug purchase and DEA approval. Information like this will further my knowledge of how a lab functions and will help to inform my decisions regarding the path I will take in my carrier as a scientist. Knowledge on how to run a lab is very important as it will allow me to understand the different aspects of being a researcher beyond experimenting and data collection. Simply understanding how to run an experiment (something I learned how to do in high school) will not be useful if I do not know how a lab works in other aspects. Publishing work is another area that I hope to further my knowledge in as that is the most important part of being a scientist. By knowing to publish scientific findings I will put myself ahead of others looking to do research as I will have a knowledge base that can propel me forward in the scientific world.

Another area of knowledge that I hope to learn is how life of a researcher is and if it is as fulfilling as it seems or if it is mostly repetitive tasks that will drive me crazy over time so to speak. This again will help me make decisions on what path I should take carrier wise. What I believe to be the overall point of the BSURF program is to acquire hands on experience in laboratory setting. It should go without saying that this is an expectation of mine as I hope to gain action-based skills in a lab.

Here is me taking a picture of the building to make sure I was at the right place