The Art and Science of Research and Development: Fueling Innovation

My blog focuses on Business/Entrepreneurship and Science, Technology, Engineering, and Mathematics (STEM). Many innovations that we take for granted today have emerged from the science world. These innovations have led to the creation of whole business sectors. The following contributed post is entitled, The Art and Science of Research and Development: Fueling Innovation.

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In the business world, research and development (R&D) is at the center of innovation. R&D acts as the analytical backbone for any organization looking to remain competitive against competitors and satisfy customer demands. But its road from conception to realization may not always be smooth. In this blog, we will look at key aspects of R&D that play such an important role in shaping a business’s future.

Photo by Diane Serik on Unsplash

The Golden Age of Curiosity

At its center lies curiosity, its source and spark for R&D innovation. R&D thrives when companies treat R&D like an exploratory playground. Companies who take an exploratory approach often experience creative breakthroughs leading to innovative products and services. However, unchecked curiosity should always be balanced against thorough analysis and strategic planning for the best results or it can quickly turn into chaos.

Data: The Tireless Sidekick

No discussion about R&D would be complete without giving data the respect it deserves. Like a sidekick in any superhero comic book story, data supports and validates your most precious ideas. High-quality data collection and analysis are indispensable components of successful R&D. Its use helps inform teams where they stand, identify new opportunities, and safeguard against unnecessary misadventures. The mantra “In Data We Trust” could well become many projects’ north star.

Budget Battles: An Eternal Showdown

Ah, budget…R&D’s perennial adversary. Allocating sufficient resources for research endeavors requires companies to play a delicate balancing act between cost-effectiveness and groundbreaking outcomes. Each step must align with organizational goals while supporting potential disruptive success. Lest their competition catch up quickly before you can say “unicorn startup”.

The Human Element: Building the Dream Team

Behind every successful innovation lies a team of dedicated dreamers and doers working nonstop. R&D success depends on their talents and skills bringing ideas to fruition. Diversity adds flavor and depth, giving rise to new perspectives that challenge existing norms. Promoting open communication, encouraging an inclusive work culture and offering development opportunities are important ingredients in creating this human recipe of success.

Technology and Equipment: The Backbone of R&D

Cutting-edge technologies and state-of-the-art equipment form the cornerstones of innovation in R&D. Technology allows R&D teams to push the limits of what is possible, providing tools that enhance precision, efficiency, and scalability. From advanced computational software that facilitates complex simulations to cutting-edge laboratories equipped with a ingaas camera for infrared imaging, these resources play an important role in turning visionary concepts into tangible products and solutions. Also, artificial intelligence and machine learning have transformed data analysis for more accurate predictions and streamlined processes. Investing in appropriate equipment not only boosts productivity but gives teams the competitive edge necessary to lead in their respective industries.

Embracing Failure: The Not-So-Secret Ingredient

R&D can often be an uphill struggle, and failure in R&D is both common and an important learning experience. Companies that view failure not as an endpoint but as an opportunity can build resilience among their teams by extracting insights from failed projects to incorporate into future ones. Don’t fear those facepalm moments, because in them lies your key to eventual victory.

Conclusion

Going through the complex world of research and development is both an art and science. An exhilarating space where creativity meets analysis, where curiosity transforms into innovation, and where investment becomes non-negotiable in businesses looking towards the future. R&D investments must not be seen as optional if you want your company to unlock untapped potential. With an engaged team, robust data, and an openness towards failure learning, there are bound to be promising innovations out there waiting to be discovered.

The Story of How I Earned My STEM Degree as a Minority

“It’s my job to prepare you for wherever you go after you leave my lab. When you go into a company, no one is going to tell you if your presentations and writings are sloppy. You won’t get promoted and you’ll never know why!”

In my post entitled, Who will benefit from Apple’s $350 billion investment?, I cited data stating that less than 10% of Science, Technology, Engineering and Mathematics (STEM) degree holders are African American – a staggering number as these are some of the highest paying careers today. With the first principle of my blog being “Creating Ecosystems of Success”, and one of my focuses being awareness of the STEM careers, I wanted to tell my story.

Thus far I’ve published posts discussing the ‘Biomedical’ sciences I’ve been trained in, ‘Regulatory’ science, the ‘Applied’ sciences, and the ‘Transferrable’ skills learned when earning STEM degrees. In these posts I’ve attempted to make these sciences easily understandable for students and families with backgrounds like my own (see the story of my blog). Potentially the most important story of all though is how one becomes a STEM professional.

I’m a firm believer in teaching the ‘how’. It’s important to encourage participation in the STEMs, but as a student who walked into my training not fully  understanding the opportunity in front of me, I think it’s also important to share what went into earning my STEM degree in a very open and honest way – the good, the bad and the ugly – no fairy tales and no magic. In this post, I’m thus revisiting both my learning points science-wise, and some personal challenges during the process as an African American male coming from Buffalo’s east side. The latter challenges may surprise you.

The majority of the visuals used in this piece are materials from my thesis. Click on any of them to enlarge them. Lastly in this piece I refer to my thesis project without getting into its specifics. I describe it in greater detail in my Basic Sciences and Basic Research post.

Learning how to do Science

I fell in love with “Life Science” in the seventh grade at Campus West in Buffalo, NY. I followed that love into Hutch-Tech High School where I majored in ‘Biotechnology’ (AP Biology). At Johnson C. Smith University (JCSU), I distinguished myself as a ‘A’ student in my core courses as a Biology major which led to my participation in the Ronald E. McNair Program, where I worked two summers in a Hepatic (Liver) Physiology lab.

It was my first time performing ‘Basic’ scientific research (see my Basic Sciences and Research post). I earned an undergraduate fellowship from the Environmental Protection Agency my last two years at JCSU. This precluded my participation in the ‘Minority Access to Research Careers’ (MARC) Program where I would’ve worked on a research project year-round, and would’ve gained more valuable experience.

Having participated in the McNair Program, I decided to pursue a Ph.D. in Pharmacology, thinking that working in a Pharmaceutical company like Pfizer or Merck would provide stable employment. Thus, the sole focus for my science training was finding a job. While a Ph.D. in Pharmacology would help me get there, I didn’t completely understand what the road to a Ph.D. in this particular STEM field entailed, as I didn’t yet know how to do science fulltime.

Rigorous Scientific Research

“Anwar has never done rigorous scientific research before,” my Graduate Advisor, a fellow Western New Yorker, wrote in my evaluation for my second lab rotation within the Department of Pharmacology of the University of Michigan. He gave me an ‘A’ which I was happy about, though based upon his statement, I wasn’t sure how I’d done in the lab. Did I perform adequately over those four months? Did I underperform, but still received an ‘A’ just because? Either way, he allowed me work under him for my thesis project – perhaps seeing some potential in me.

What made me want to stay in his lab? After my summers in the McNair Program, I knew something about the enzyme my Graduate Advisor’s lab worked on; “Neuronal Nitric Oxide Synthase” (see my Basic Sciences and Research post). I was also encouraged by two more senior students in another lab to stay based upon my advisor’s: talent, his productive track record and the productivity of his students.

By the way, in the coming years when prospective students would visit our department, my Graduate Advisor was always very adamant about the prospects getting the current students’ perspectives on the department. I think his reasons were that doctoral research is a significant life and time commitment as you’ll see later, and it’s in a student’s best interest not to walk into a department ‘blind’. Ideally, they should have a feel for the overall climate of their prospective department; its culture, its faculty and whether its students go on to establish their own careers.

The Basic Sciences and Research

The Basic Sciences and Basic Research are worlds all in themselves, worlds I initially didn’t know how to succeed in. Aside from some of my teachers in high school, there were no STEM professionals in my ecosystem in Buffalo. Also, once again, while my summers in the McNair Program gave me a taste of this new adventure I was embarking upon, they didn’t show what the experience would be like fulltime.

What qualities and attributes were needed to earn my Ph.D. in the STEM field I had chosen? One very important quality/value I received from my home ecosystem was that of hard work and the importance of doing quality work. I’ll credit my mother for this and her many years of making us do chores at home, which instilled a sense of personal responsibility and pride in my work. Also, the adversity-filled experience on my high school basketball team taught me how not to quit on things when they got hard – another valuable tool. Lastly, I was always naturally very malleable personality-wise, and open to being taught.

My Dad’s words about excelling in my coursework helped me to get into Graduate School and were useful until the end of my coursework. Once the fulltime research phase began however, it was a whole different ballgame, as working for my Graduate Advisor required a host of other ‘tools’.

I myself was a ‘project’ going into my Graduate Advisor’s lab – one which needed to be built from the ground up. There were plenty of challenging times for both of us as my first two to three years were spent literally just figuring things out. Fortunately, he was willing to teach me as long as I was willing to do the work and be taught. What do I mean by figuring things out? The following is a summary of what I learned as I worked on my thesis project:

Learning to ask Questions, to be Inquisitive and to Talk about Science

I added this learning point in last, but it may be the most important of all. I’ll credit the whole department for teaching me this lesson. One classmate and one professor stand out here. Verbally asking questions is essential to doing science. In my Basic Sciences and Basic Research post, I described how our experiments were questions themselves, but it’s also very important to be able to verbally ask questions of peers about their science both one on one, and in group settings in a respectful way.

During graduate school, I sat in on numerous seminars, and I was initially afraid to ask questions in front of everyone else. Part of it was a fear of sounding foolish. The other part of it was that while I’d excelled in my coursework as an undergraduate, I didn’t regularly talk about science with my classmates at my undergraduate institution. Over time I overcame my fears and got to the point where getting my questions answered superseded everything else.

Seeing and Understanding the Science through my Advisor’s Eyes

“You’re going to have to drive the project!” My biggest learning point was learning to see the science through my Graduate Advisor’s eyes, and not just in terms of obtaining my Ph.D. and finding a job. There was an ‘art’ to science, a thought process, a methodology, a culture and a lifestyle. It took about five years of training to get to the point where I could start see the science the way he saw it, and even talk about my project the way he talked about it.

I needed to understand the science in its entirety and appreciate the process, and all the challenges involved. I needed to approach my research like a professional; to design my experiments systematically and proactively – to think about the limitations of our experiments and the data we generated, to think of the next steps, and to always think about the final published paper.

Doing Science in the Lab Everyday vs. Learning about it in the Classroom

There’s a major difference between learning about science in a classroom setting, and actually doing quality science fulltime. For me that involved being proactive about my work, and being consistent in everything I did experimentally, in my writings and my presentations. Our experiments were questions, the results were the answers, and we needed the answers in a timely fashion. Everything needed to be approached with a sense of urgency, and in a way, time was our enemy. It also involved thinking about the project when outside of the lab – something my Advisor and his peers and competitors did – sometimes at the expense of other things.

I was now out on the edges of science in the ‘trenches’, trying to discover new knowledge. A major part of this involved approaching my thesis project like a job. And in many ways it was, as my peers and I received stipends. It wasn’t a high-paying job in terms of salary, but instead the payment was knowledge and wisdom which would equate to greater financial compensation later.

Graduate Research is in part a Job or an Apprenticeships line one of the Skill Trades

“This is your job now!” My Graduate Advisor and I had this conversation after my completing two years of coursework and starting my thesis project fulltime. I hadn’t made the connection yet that my research involved being in the lab 100% of the time. It required being on time in a job-like setting where I’d work on my project daily at a work bench – sometimes at night and on weekends. The data generated from my project would be published in scientific journals, as well as when my Graduate Advisor sought to renew his own research grants. Finally, it would be the basis for my completed dissertation, in addition to a record of my productivity after eventually leaving his lab.

Learning to Multitask

I had to learn to work smart, and not just hard. My Graduate Advisor instilled in me the ability to multitask and to, “have multiple things going at once,” as he always emphasized. In addition to working on my own project, I was also responsible for growing the stocks of proteins that the entire lab used, which was a huge responsibility. I was also the lab’s “Chemical Safety” officer who was responsible for all the lab’s waste disposal – chemical and radioactive. Multitasking was what he did on a grander scale all year. As a student, it seemed unfair at the time, but it’s a skill that has transcended our lab into other arenas, as with everything he taught us.

Learning to Compete and the Culture of Science

“You have to know where the line is, and then do your best to stay above it,” my Graduate Advisor told me years later after I graduated. Though I didn’t understand it at the time, he was teaching his students how to compete and survive. It’s not widely discussed, but science is about competition, especially in academia where at any given time, multiple labs around the country, and even around the world, are working to make the same scientific breakthrough. It’s an arena where ultimately, the group who makes the finding first gets the fame and notoriety, and future grant funding.

There was such a thing as being ‘scooped’. This is when another lab made the finding first, leaving its competitors to either disprove it, to add something to it, or to work on something else altogether. Because my Advisor was so talented and hungry, it never happened to us, but I saw it happen to some of my peers and their labs. Nothing was guaranteed. Just like he had to fight and claw to keep his lab running, I also had to fight and claw to push my project through to completion. I further had to fight and claw to stay in the department and finish my degree. Science and life are about competition.

“I know that I drove you guys pretty hard,” my Advisor shared with me years after I graduated, which we both smiled about. At times he was very abrasive, aggressive and very demanding of us. It was for a reason though and I realized during my training that working for brilliant and driven people is hard, but if you can stay in the process and take their coaching, you’ll be better off for it later.

Driven by Their Research

My Graduate Advisor attended the Massachusetts Institute of Technology (MIT) as an undergraduate, the University of Michigan for graduate school, and then the National Institutes of Health (NIH) for his own postdoctoral training before becoming a professor at the University of Michigan. We never talked about MIT in my ecosystem in Buffalo, and I just started understanding my Advisor’s pedigree towards the end of my training. His father was a scientist as well, and he thus had exposure to science at an early age, and even earned a couple of patents before starting college. Don’t get me wrong, having parents in the STEMs isn’t a necessity to getting into one of the fields yourself, but the early exposure can pay huge dividends later.

This is a good place to state that my Graduate Advisor, his peers, and scientists at most research universities are driven by their scientific research, and they’re always thinking about it; late at night, and even on family vacations. The argument can be made that their research is their purpose for living. The truly talented ones are further tough enough to withstand any environmental changes such as when the second Bush Administration cut the NIH’s budget, causing many labs around the country to downsize or perish altogether, while others figured out how to survive.

“You all are very different than we were! When I was a graduate student, we fought over the latest issues of the Journal of Pharmacology and Experimental Therapeutics (JPET),” said one of the more senior and celebrated faculty in our department who was jokingly said to have invented the Heart. He felt that we weren’t studying up on our field enough in our spare time beyond our core curricula. Most of us were only doing the minimum reading and studying, something my Graduate Advisor also stayed on me about during my training.

Learning to Manage my Life outside of the Lab so that I could do Science

Learning to manage my life outside of the lab so I could do science

The accompanying newspaper clipping is from one of Buffalo’s local weekly black publications, The Challenger. My mother proudly submitted the story and that’s her handwriting on the top of the clipping. It was a big deal back home and she even shared with me that I’d exceeded her expectations which was very gratifying. When looking at the clipping, it’s something to proud of, but what you don’t see there is that there were a host of personal learning points outside of the lab as well – experiences which could’ve derailed the whole thing.

Being African American and ascending in education and a career often leads to discussions of “forgetting where you came from”. So, I want to close with what I learned about how life outside of the lab can affect one’s ability to do science and be a professional. Sometimes it’s actually necessary to leave certain parts of your old life behind. I learned on numerous occasions during my STEM training that I had to protect both my project and my life. That is, I had to make strategic decisions in my personal life that would increase my chances of finishing my degree and surviving to talk about it.

While working on my thesis I got involved in a very chaotic romantic relationship which compromised my mind, spirit and overall well-being at times; nearly derailing my project and potentially adversely affecting my Graduate Advisor’s entire lab all at the same time. There was one day I consider a near death experience – something I’ve discussed with friends and relatives only in bits and pieces. Fortunately, I survived, but this type of thing wasn’t restricted to my significant other.

There were two instances involving two close friends whom I consider my second and third brothers. One incident transpired over a Thanksgiving holiday and the other a Christmas holiday – both of which involved nearly getting pulled into violent confrontations late at night at nightclubs and parties in my hometown of Buffalo, NY. One friend had too much to drink and in the process of having his own fun, inadvertently splashed another guy with his beer. The guy who got splashed was unhappy about it and started following us around the venue. While I thought bullets might fly, my friend got away with just getting punched and knocked out temporarily. Fortunately, we both made it home safely.

In the second incident, another buddy wanted to stay and confront some guys over a female outside of a nightclub. Apparently, he was looking at the guy’s lady and there was an initial confrontation I didn’t see inside the venue. My friend didn’t want to appear afraid and wanted us to take our time leaving. When I realized what was going on, I wanted to leave immediately – something he and I clashed over afterwards. Fortunately again, nothing happened, and we got out of there safely.

Neither of these incidents were worth the potential price to be paid. Neither my significant other, or either of my friends considered the possibility of my showing up to the lab in a cast, with a black eye, or with teeth missing, or maybe being laid up in a hospital, unable to continue my research. The take home message from all of this is that you must be your own best advocate in life. None of us can avoid tragedies, but there are some things we can avoid.

You must protect what you’re doing, sometimes from people around you in your family circle, friends or significant others, because someone else’s selfishness and bad decisions can hinder your life and professional aspirations. In my case it was earning my STEM degree and starting my career.

Closing Thoughts

“Give a man fish and you’ll feed him for a day. Teach a man to fish and you feed him for a lifetime.”

I included this famous quote from the Chinese Philosopher Lao Tzu because the road to my STEM degree was literally like learning how to fish. The opening quote from this piece is from one of my many talks with my Graduate Advisor. In some ways our relationship evolved into that of a father and a son which I’m very, very grateful for as not every student had this. I saw several peers leave partway through their graduate training without their doctorates either due to a loss of hope, or irreconcilable differences with their advisors. Some were African American, but not all were.

This is my STEM story and there are many others out there. I want to point out that the point of telling this story was not for my glorification. As I said in the opening, I think it’s critical to explain all sides of the process in addition to simply encouraging students to get involved in the STEMs solely because of our under-representation as African Americans, and because of the monetary benefit. The how is very, very important. If you’re a STEM professional, I encourage you to also tell your story to STEM-hopefuls in an age-appropriate way.

I’d like to end this story by acknowledging the late Dr. Minor J. Coon.  Dr. Coon was not only a member of my Thesis Committee (on the program above), but he was also a legend and a pioneer the in the study of Phase I Drug Metabolizing Enzymes – Cytochrome P450s particularly.  Dr. Coon actually trained my Graduate Advisor who subsequently suggested asking Dr. Coon to be on my committee – something that surprised me as we all looked upon him with great reverence.  Growing up on Buffalo’s east side, I never dreamt of being a part of such a well accomplished tree of scientists.

Thank you for taking the time to read this blog post. If you enjoyed this post you may also enjoy:

A look at STEM: What are the Basic Sciences and Basic Research?
A look at STEM: What is Regulatory Science?
The transferrable skills from a doctoral degree in the basic sciences
A look at STEM: What is Inhalation Toxicology?
A look at STEM: What is Pharmacology?
A look at STEM: What is Toxicology?
A look at STEM: What is ADME/Drug Metabolism?

The Big Words LLC Newsletter

For the next phase of my writing journey, I’m starting a monthly newsletter for my writing and video content creation company, the Big Words LLC. In it, I plan to share inspirational words, pieces from this blog and my first blog, and select videos from my four YouTube channels. Finally, I will share updates for my book project The Engineers: A Western New York Basketball Story. Your personal information and privacy will be protected. Click this link and register using the sign-up button at the bottom of the announcement. If there is some issue signing up using the link provided, you can also email me at [email protected] . Best Regards.

A Look at STEM: What are the Basic Sciences and Basic Research?

“In addition to understanding the fundamental principles of one’s field, a major part of understanding Basic Research and Science is understanding the instruments and technologies used.”

One of the focuses of my blog is awareness of the Science, Technology, Engineering, and Mathematics (STEM) fields. Thus far, I’ve written posts covering the “Biomedical Sciences” I’ve been trained in including: Pharmacology, Toxicology, ADME/Drug Metabolism, and Inhalation Toxicology. I’ve also written a post discussing “Regulatory Science” in the Public and Private sectors, in which I discussed the “Applied Sciences” and “Research and Development”. In this post I want to discuss the “Basic Sciences” and “Basic Research”, the foundations from which we receive all our new scientific knowledge.

The foundations of any of our commercial scientific and technological innovations are the Basic Sciences and Basic Research. A simple Google search led me to a site which stated that the four major Basic Sciences are: Biology, Chemistry, Mathematics and Physics. Many people consider Physics to be the ‘Grandfather’ of all the sciences because each of the others rest upon its shoulders in some way. Any of the other Basic Sciences fall under one of these four branches.

For Biology for example, many of the sciences underneath its vast umbrella include: Biomedical Sciences, Agricultural Sciences, Environmental Sciences, etc. Within the Biomedical Sciences there are the sciences I’ve written about, as well as: Cellular and Molecular Biology, Genetics, Microbiology, Virology, etc. The same is true for Chemistry under which there are: Analytical Chemistry, Organic Chemistry, Physical Chemistry, etc. While Physics is its own discipline with its own subdisciplines, as you’ll see later, its principles permeate throughout the other major sciences, especially when you’re carrying out ‘Basic’ scientific research.

Basic Research is simply the pursuit of new knowledge and the understanding of a specific area of focus. As described throughout my blog, my Ph.D. is in Pharmacology, with two and a half years of training in its sister science, Toxicology. In the Basic Research world scientists known as ‘Principal Investigators’ run labs at major research institutions, like the University of Michigan, where they have specific research areas of interest.

Principal Investigators ask specific research questions in their areas of focus through their research projects. They arrive at their answers for these questions through experiments and report their results in papers published in scientific journals. To carry out their research, which I’ll describe later, Investigators usually receive grant funding from federal sources such as the National Institutes of Health (NIH), or from the Private Sector. As you’ll see there is a business side to research, both in academia and in the private sector.

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As described in my Pharmacology post, there are numerous sub-disciplines within Pharmacology. My Graduate Advisor’s area of focus was ADME/Drug Metabolism which involved some aspects of Biochemistry and Cell Biology based upon the questions he was asking. For the remainder of this post I am going to discuss my thesis project in his lab to give readers a feel for what Basic Research is and why it’s important. Some of the terms I’m going to use will be on the esoteric side, but I’m going to do my best to keep the discussion as simple as possible.

The title of my thesis project was the “Labilization and Proteasomal Degradation of Neuronal Nitric Oxide Synthase” – a mouthful for anyone unfamiliar with the field. If you google me, you’ll find two ‘first author’ publications that I published in my Graduate Advisor’s lab with the assistance of my lab mates; fellow students, postdoctoral scientists, senior scientists, and technicians. I’m crediting the entire lab because, while I was the first author on these papers and it was my thesis project, my colleagues also contributed their expertise and man-hours. Everything in our lab was done as a team. I also contributed to my lab mates’ work. My two first author publications are:

Ubiquitination and degradation of neuronal NO-synthase in Vitro: Dimer stabilization protects the enzyme from proteolysis published in Molecular Pharmacology and;
Tetrahydrobiopterin protects against Guanabenz-mediated inactivation of neuronal nitric oxide synthase in Vivo and in Vitro published in Drug Metabolism and Disposition.

What does all this mean? In simple terms, our bodies are made up of numerous organs, systems and tissues. These are, in turn, made up of cells, nucleic acids and proteins which do the work on the ground level in our bodies. When we become ill, infected with a bacterium or a virus, poisoned by a toxicant, or develop cancer, there’s an underlying biochemical change that has occurred on the cellular level. It could be the enhanced production of viral particles, DNA damage leading to tumor formation, inhibition of an enzyme’s function, or the breakdown of key cell signaling pathways.

In Type II Diabetes, for example, the cells of our bodies become nonresponsive to endogenous ‘Insulin’, which naturally allows them to take up glucose from our bloodstreams. The breakdown of this intracellular signaling pathway leads to the hallmark maladies associated with Type II Diabetes. Pharmaceuticals likewise exert their therapeutic effect by modulating these same cellular processes. But how do these processes occur? And how do pharmaceutical companies design drugs we use to treat diseases? The answer is Basic Research.

My Graduate Advisor, a Pharmacologist and a Biochemist in training, was very interested in how exogenous chemicals could selectively control the fates of proteins within cells. Prior to my entering in his lab, he discovered that an anti-hypertensive drug called ‘Guanabenz’ could inhibit the metabolic activity of the protein “Neuronal Nitric Oxide Synthase” (nNOS), and then cause the loss of the protein itself in rat penile tissue. Other chemicals also inhibited the protein’s activity but didn’t cause a loss of the protein. So again, there was something unique to each chemical and their effect on the protein in the cell. There was a trigger that made the protein go away in certain instances. But how was this all happening?

In my earlier posts, I discussed how animals are used as models for studying human health based upon shared organ systems and metabolic pathways. My thesis project investigated this phenomenon in rat penile tissue using an in vitro system, meaning that it all took place in test tubes in a ‘cell-free’ system where we could mimic the cellular environment and control the conditions of our reactions. This allowed us to ask questions we couldn’t ask in cell or animal models.

My first finding was that our protein of interest had to undergo a major structural change for it to degrade. Chemicals like Guanabenz triggered this structural change by causing the breakdown of the homo-dimeric active protein form to its inactive monomeric form. Other chemicals prevented this structural change and protected the protein from degradation. What was even more fascinating was my second finding. This structural change was triggered by loss of a specific intracellular Cofactor which was important for maintaining the homo-dimeric form of the protein. It was the loss of this cofactor that triggered the subsequent toxicity in the rat penile tissue.

My project was a very ‘mechanistic’ project in that we were going down into the ‘weeds’ to figure out how the effect in the whole animal occurred. Why was this important and what could be done with this information? Several things. It could be used to create new drug targets, and it could also be used to predict and understand similar toxicities by chemicals with similar structures. These are all things Chemical and Pharmaceutical companies, and Regulatory Agencies consider when bringing new products to the market and when protecting human health.

During my thesis I performed ‘Bench Science’. I literally had a work bench and performed experiments every day, working to generate quality data I could publish. As I worked to answer my research questions, I also learned a wealth of research techniques and technologies, in addition to learning how to perform scientific research (discussed in the next post). While it was a biological project in nature, my thesis project involved the use of numerous analytical chemical tools and technologies, many of which involved some understanding of Chemistry and Physics.

In this section I’m going to introduce a few terms commonly used in the research world which were foreign to me when I started. ‘Assay’ for example, is just a fancy term for an established and widely used experimental method. The others will be explained throughout and should be easy to follow. The devices and technologies described are hyperlinked.  The methods, tools and processes I utilized during my research included the following:

Cellular and Molecular Biology techniques: We used numerous cell models to: generate large quantities of our protein of interest for our in vitro experiments, and we had other cell lines to ask questions about the fate of the protein within cells. The latter involved inserting (transfecting) the DNA of the protein of interest into cells. This involved the use of Cellular and Molecular Biological techniques, and the use of Cell Incubators and, in some instances, Orbital Shakers to culture (grow) the cells, depending on the cell line.
Stoichiometry: This key aspect of General Chemistry was a critical part of all our experiments. Specifically, it was central in the calculation of ‘Molar’ concentrations when preparing the numerous ‘Chemical Reagents’ that were used including: buffers, cellular media, solvents, matrices, resins and so on.
Column Chromatography and Protein Purification Methods: We used numerous protein purification methods, particularly Affinity and Size Exclusion chromatographic methods to create clean preparations of our proteins of interest and other preparations. This allowed us to study its activity in isolation, its protein levels and ask questions about any structural changes.
Gel Electrophoresis and Protein Detection Methods: We used electrophoretic and antibody-based detection methods for measuring actual protein levels for visual analysis and quantification. The bread and butter technique of my experiments was called the ‘Western Blot’ analysis, whereby the proteins in my in vitro assay were separated by size, then detected, and finally, quantified using a radio-labeled antibody. One of techniques used in the lab was the Protein Assay, which allowed us to quantify the amount of protein in various preparations using a 96-Well Microtiter Plate Reader; arguably the workhorse for not just our lab, but also for neighboring labs. The Microtiter Plate Reader contained a Diode Array that measured changes in absorbance which helped inform us of the concentrations of the protein preparations (Beer’s Law). One of the 96-Well plates used in the Microtiter Plate Reader is picture below without any dyes or solutions.
Enzymatic Activity Assays: We used numerous assays to measure the activity of our protein. The primary assay used for measuring the activity of the protein was the “Oxy-Hemoglobin Assay” where we measured the conversion of Oxy-Hemoglobin to Met-Hemoglobin. We used this conversion to quantify the amount of Nitric Oxide produced by our protein with and without inhibitors/inactivators. This assay relied u9pon measuring changes in absorbance and thus, once again, the Microtiter Plate Reader was the primary tool for asking questions about the activity of our protein of interest. In some instances, other methods were used to measure activity as described next.
Physical and Analytical Chemical and Detective Methods: Consistent with most ADME/Drug Metabolism labs, a tool we heavily relied upon was High Performance Liquid Chromatography (HPLC) – a classic detection tool used for measuring the following: cofactors, molecules, metabolites, and proteins; based on their chemical properties and how they behaved in specific organic and non-organic solvents. Later in my thesis project, our lab purchased several Mass Spectrometers, which is the most sensitive chemical detection tool. However, my projects didn’t require me using them.

In addition to understanding the fundamental principles of one’s field, a major part of understanding Basic Research and Science is understanding the instruments and technologies used. As the researcher, understanding these technologies is critical to understanding what your data are and are not telling you. If you’re listening to a peer’s seminar, or reviewing their publication, understanding the technologies also helps you understand their work. In some instances, a researcher’s understanding of the technologies gives them ideas about combining them to ask unique questions.

What’s the measure of how good a scientist is? It’s their publication and funding records. The top scientists and their labs continuously come up with good ideas, then publish their work in competitive scientific journals. When scientists continually come up with good ideas and continue to publish quality work, they’re more likely to continue to secure funding and ascend in their field. The reciprocal is true for scientists who don’t come up with good ideas and don’t publish.

It’s worth noting here that the rules for publishing are different in the Private Sector vs. Academia. Research projects in the Private Sector are usually geared towards innovation and selling a product. As a result, research findings are considered ‘Intellectual Property’ which companies own and may not want to disclose out of fear of losing a competitive advantage to other companies in their sector. The research projects are also very focused, and the scientists have less freedom in terms of what they can work on. Employment is also heavily dictated by that particular company’s economic health and overall direction.

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A byproduct of training in the Basic Sciences and performing Basic Research is acquiring the knowledge and expertise which the Applied Sciences and the Private Sector use to bring new products to the market. The training can also be used to form Consulting groups (see my Regulatory Science post). If a scientist is thoroughly trained, he or she will also acquire a separate set of skills described in my blog post entitled; The transferrable skills from a doctoral degree in the basic sciences. In my case, the discipline was Pharmacology, but this applies to pretty much any of the other Basic Science and Basic Research disciplines.

How long can it take to earn a degree in a STEM? It depends on the STEM area. The path I chose took roughly 5-6 years. That length of time was impacted by my first learning how to do research (discussed in my next post), and then working through the complexities of my project. If the systems and tools for asking your scientific questions are already established, then it’s a clearer path. If you’re establishing your methods for the very first time though, it could take a little longer.

If you’re building upon someone else’s work, you must also hope that they’ve reported their methods and results honestly and accurately. If so, their work will be easier to reproduce. The hard part when doing Bench Science is that many experiments don’t work initially, and it can take time to get your systems to the point where you can start generating quality, publishable data. During my thesis, I easily performed hundreds to thousands of experiments. It took time to establish my systems and their conditions, and then it took more time to generate quality, publishable data to answer my scientific questions.

Having role models is critical when training in the basic sciences. Your graduate advisor typically plays this role. Why is it important to have role models? Having inspirational figures to look up to whilst studying can be extremely important. They can provide motivation, career guidance, representation, and inspiration. These can serve as examples of what can be achieved with hard work and dedication, and they can provide invaluable advice on navigating the industry’s challenges. In addition, people who have managed to earn their way into the science industry by their own merit, such as Monica Kraft Duke Settlement, can be great motivators and inspire you to create your future.

The Basic Sciences and Basic Research are vast. This post just focused on one aspect of Pharmacology – a Biomedical Science. Whether it’s a: pharmaceutical, an industrial chemical, a medical device, a GMO crop, a Blockchain Technology application, or one of Elon Musk’s new SpaceX rockets, someone had to do the underlying research which gave rise to the innovation. I’m going to close by reiterating something from my Pharmacology and Toxicology posts, which is that each Basic Science has its own professional society and annual meeting. Thank you for taking the time out to read this blog post. I hope I was able to give you an understanding of Basic Sciences and Basic Research.

The next posts in this series will talk about my personal journey towards becoming a Scientist and earning my STEM degree. If you enjoyed this post you may also enjoy:

A look at STEM: What is Regulatory Science?
The transferrable skills from a doctoral degree in the basic sciences
A look at STEM: What is Inhalation Toxicology?
A look at STEM: What is Pharmacology?
A look at STEM: What is Toxicology?
A look at STEM: What is ADME/Drug Metabolism?

The Big Words LLC Newsletter

For the next phase of my writing journey, I’m starting a monthly newsletter for my writing and video content creation company, the Big Words LLC. In it, I plan to share inspirational words, pieces from this blog and my first blog, and select videos from my four YouTube channels. Finally, I will share updates for my book project The Engineers: A Western New York Basketball Story. Your personal information and privacy will be protected. Click this link and register using the sign-up button at the bottom of the announcement. If there is some issue signing up using the link provided, you can also email me at [email protected] . Best Regards.