Aesthetic appreciation

aesthetic appreciation

A story on how borderline sexual harassment in the form of “aesthetic appreciation” can drive young female researchers out of the lab –

Day 1: A new male grad student comments on a young female sophomore undergrad in the lab about the sweet smell of her perfume.

Undergrad feels awkward but ignores the comment at first. Of course, telling something that they smell good is not creepy. It is the connotations that changes everything. Especially if it is the older male grad student telling a young, naive female undergrad with no other lab members around. This is about the power dynamics that come into play and the context of the comment. A person’s smell has been associated with attraction and intimacy.

Several days later: Male grad student inquires why the undergrad isn’t wearing her typical sweet perfume that day.

Undergrad feels uncomfortable but lets go for the second time. She is shy and soft spoken. She is only a teenager in a lab full of older grad students and post docs. She is the only female working in a lab surrounded by male colleagues.

Days in the future: The male grad student starts commenting on the undergrad’s perfume, the way her hair was tied up the previous day but is left out today, her red top worn last week and other clothing choices.

Undergrad decides not to continue pursuing research in the lab due to her feeling constantly uncomfortable in the workplace. No one else in the lab has any idea about what transpired.

The act of “aesthetic appreciation” (from Cooper’s 6 Levels of Harassment) can be considered as borderline sexual harassment. Context is always important and so is the power dynamics in play. If the receiver of the compliment feels uncomfortable, then it is most certainly NOT OK! One may never know the true intentions of the male grad student but seems like he is quite ignorant of the general social cues that are acceptable and those that are not acceptable.

Young female undergrads need to realize and understand that situations like these are serious and can become more and more aggressive over time if the “complimenters” are not called out for their unwanted appreciation. Young female researchers need to seek out mentors in and outside the lab that they can trust and confide in. More importantly, if and when they feel like their personal space is being invaded, they need to call out other people’s bullshit when they encounter them. At the end of the day, a laboratory is a professional workplace and should follow the same rules and policies as enforced by many non-academic workplaces.

The role of the principle investigators (PIs) and advisors in such situations is complex but very important. PIs need to instill strict rules about sexual harassment and the dominant male patriarchal practices in the lab. Unfortunately, many PIs believe that science is greater than the scientist i.e., many sexual and racial microaggressions and other similar practices get pushed under the rug because “science is the universal truth and nothing else matters“. Unfortunately, science is done by humans and one shitty scientist can cause a ripple effect and eliminate many young, promising scientists – especially women from even entering the turf.

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Mental health awareness month

I opened my email this morning to see a message from my department with the subject line “mental health series”. May is the mental health awareness month and our department is organizing a series of events targeted towards mental health and the kickstart event is a “mental health break in the form of a Popsicle social” (other events being organized include beginner yoga sessions, etc). Reading this email made me think about the important roles that universities and graduate programs play in spreading awareness about mental health issues in academia and in weeding out the stigma surrounding this issue in a professional setting.

Mental health in academia is no joke. MANY studies have highlighted the stress and depression experienced by graduate students and researchers in academia. How big of a problem is this, you ask? From a Nature study of 2,279 students from 26 countries and 200+ institutions:

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Nature Biotechnology 36, 282–284(2018) doi:10.1038/nbt.4089

During the first week of graduate school, we are made to attend a series of safety, teaching, research, etc information sessions. Nothing is said about tackling mental health or dealing with depression during these orientation sessions. What are the resources available on campus (if there are any in the first place)? How does one deal with constant failure and disappointment in grad school? How does one deal with isolation and loneliness during one too many 16-hour days? How does one deal with work-life balance or should that be thrown out of the window? What are the realities of academia that are not openly talked about in the fancy brochures and newsletters? Perhaps the incoming first year students are too naive to realize what lies ahead of their graduate school careers. But what about the senior students? What is being done to address this issue amongst the 2nd, 3rd, 4th, and the 5th year grad students?

Graduate students should not be ignored and definitely deserve some sort of a counseling or orientation on tackling mental health issues during our time here.  We need appropriate resources to be able to reach out in time of need. This is an ongoing conversation and should not be limited to one day or even one month. We need senior students as well as professors who are compassionate mentors, we need counseling resources specifically targeted towards academia, we need to educate our community about the stigma around depression, anxiety, etc along with the realities of mental health, and so much more.

More on the mental health crisis in academia –

  1. More academics and students have mental health problems than ever before
  2. Academics ‘face higher mental health risk’ than other professions
  3. I wish we could talk more openly about mental health in academia

The Purdue Lecture Hall Series

Earlier this semester, I was invited to speak about my research at The Purdue Lecture Hall Series (TPLHS). TPLHS is an evening seminar series for high school students, teachers, and parents from the Greater Lafayette community organized by the Purdue Institute of Inflammation, Immunology and Infectious Disease (PI4D) in partnership with Mr. Joseph (Joe) Ruhl from Lafayette Jefferson High School. The series celebrates the work of a wide variety of the life scientists that represent the different areas of research within PI4D and it is meant to inspire high school students to consider life sciences as a career choice.

I began my talk by delving into my background in STEM — from high school and undergraduation to my Master’s research experience and starting my doctoral research at Purdue. I spoke about the brain and drug discovery for neurological disorders. I introduced the students to brain immunity and the role of microglial cells in phagocytosis and inflammation during Alzheimer’s disease. During the course of the talk, I also introduced the two undergraduate students who work closely with me in the lab since I was informed that many high schoolers in the audience were interested in pursuing undergraduate research while in college. This was a great opportunity to talk about how different labs on campus function and how one should go about getting involved in research early on during their undergraduate studies. Overall, this was a great experience since it made me step out of my comfort zone (which involves very little interaction with the general public) and also hopefully inspired a few students to be curious about science and research!

 

Science vs. the scientist

A common thought in the entertainment industry is whether an artist and their art can be held in mutually exclusive standards. Do you like a song because you like the musician or do you like a musician because you like their song? Can the two be separated from one another? People boycott Woody Allen films because they do not want to support his career or his power in the entertainment industry. By watching his movies, do we validate his actions by contributing to his growth as an artist? Same goes with Harvey Weinstein and many others.

Similar parallels can be drawn with scientists and their science. For example, James Watson may have contributed to one of the most significant discoveries in science -the discovery of the double helix structure of DNA- or may have led a great scientific undertaking with the Human Genome Project, but relinquished his reputation when his racist and sexist remarks were made apparent. Lawrence Krauss (theoretical physicist, cosmologist, famous atheist, and a “liberal crusader“) was recently accused of sexual harassment which was followed by more allegations and expose by female academics on social media. I have thoroughly enjoyed Krauss’ popular science opinions as well as supported his science and public policy advocacy in the past. The recent allegations and accusations have left me transfixed about whether his work deserves my support at this point. Will I (indirectly) validate Krauss’ ghastly actions by supporting his scientific literacy and the skeptic movement? The deep dark spaces on the Internet harbors more stories about prominent scientists. Do scientific contributions become less significant due to the scientists’ reprehensible actions and behavior? One may argue that science is larger than one individual where do we draw the line?

The fact of the matter is that scientific principles, discoveries, and inventions do not stem from one individual. The credibility of scientist is validated by several other scientists in charge of legitimizing the science with a proof of approval. Does continuing to fund and support such researchers mean validation of bad behavior? The forthcoming ripple effect and propagation of a toxic environment will eventually affect others in the community. Science is scrutinized and validated by peer review over and over again. Is it time to scrutinize and peer review scientists as well?

More: Harassment case opens dialogue and When will science get its #metoo moment?

Officially a PhD Candidate!

On November 16th, I successfully defended my original proposal in front of my preliminary committee and officially became a PhD candidate! I was looking forward to this day all through the summer and fall. [I have written about the entire process of our preliminary examination in my previous blog post.] I submitted my written proposal a month before my oral defense date and received feedback from my committee about the experiments proposed and the validity of my hypothesis. I am extremely grateful for each and every one of my preliminary committee members for taking the time to review my proposal and for providing their valuable feedback and criticism. This entire process helped me grow as a scientist and helped me think and write critically. I am also grateful for my family and friends who took the time to review my proposal, attended my practice talks, and provided useful comments.

As mentioned in my previous post, our graduate program requires us to pick a topic outside our main research area and develop an NIH-style original proposal related to the chosen topic. I chose to study the role of Myeloid-Derived Suppressor Cells (MDSCs) in Type 1 Diabetes (T1D). MDSCs are a heterogeneous population of immune cells that suppress or down-regulate the effector T cell responses in various immune microenvironments. In tumor microenvironments, T cells help kill the tumor cells and prevent the tumor cells from growing. However, MDSCs suppress these T cells and prevent them from killing the tumor cells thereby causing the cancer cells to proliferate. An autoimmune microenvrionment is opposite to the tumor microenvironment. In T1D, the T cells become autoreactive i.e., the T cells start killing the innocent insulin-producing beta cells in the pancreas. This leads to reduced insulin production and increased glucose in the bloodstream in the body. Insulin is an important hormone that helps in the transfer of glucose molecules into the cells that can then serve as the energy source for the cells and tissues. The destruction of the pancreatic beta cells therefore leads to an imbalance in the glucose homeostasis in the body. In such a microenvironment, we require MDSCs to suppress the T cells and prevent them from destroying the beta cells in the pancreas. The first question to ask here is, are MDSCs induced during T1D? The answer is yes. It was shown in 2014 that T1D patients have an increased MDSC induction in their peripheral blood. As to the best of my knowledge, this is the ONLY study that focusses on the native (body’s own) MDSCs during T1D. However, not much is known about the MDSCs and the different subpopulations of these cells that exists that are responsible for interacting with T cells in the pancreas. MDSC subsets and their mechanism of action are dependent on the specific tissue or the site of inflammation. Understanding the role of MDSCs in T1D and the specific MDSC subsets involved in T1D lead to several questions. I chose to investigate a few in my proposal:

  1. If MDSCs are induced in T1D patients, why are they unable to suppress the T cell responses in the pancreas? i.e., Are MDSCs defective during T1D?
  2. What are the specific subsets of MDSCs induced during T1D that are specific to the pancreatic microenvironment? MDSCs are incredibly heterogeneous and can exhibit several phenotypic and molecular states. These subsets are unique to the local tissue microenvironment.
  3. What is an MDSC-specific immune regulatory molecule and its corresponding pathway implicated in T1D that may contribute to disease pathogenesis? 

Without going into the details of each question posed, I proposed several experiments and techniques ranging from single-cell RNA sequencing analysis of the MDSC populations in the pancreas to generating MDSC-specific conditional gene knockout experiments in mice to answer these key questions. There were a few flaws in my experiments that were brought up during the presentation and I tried to address them to the best of my ability by proposing alternative approaches. Overall, my committee members were impressed with the breadth of background knowledge and experiments presented. The most important factor was to develop a hypothesis-driven proposal with a solid premise to back my hypothesis. The presentation didn’t feel one-sided and eventually developed into a curiosity-driven discussion.

Transitioning from a PhD student to a PhD candidate is a backbreaking process. Perhaps it is meant to be this way. Even though I felt numb for a few hours after the conclusion of my presentation, I could feel the academic apocalypse building up in a cloud over my head already. Here’s hoping for more successes and vital experiences in the future!

Religion, science, and believing.

I don’t usually talk about my personal views on this blog. However, this topic is something that I have contemplated for a while now and think is fair to be open about. I am still learning and evaluating my outlook on approaching this subject. Below are some bits revolving around the themes of religion and personal belief systems that were hidden away in my drafts folder for a long time. I have decided to publish all of them together. I’m sure I’ll have more to say about this topic in the future, but here’s a start.

***

Recently, I had a conversation with a fellow grad student about religion and his personal beliefs. Most academics shy away from this discussion in a professional (and sometimes even in a personal) setting. It is considered uncommon or rude to talk about it and people keep it to themselves. It is often acknowledged that as scientists, “we do science for science’s sake”, or that “a person’s religious beliefs has no place in his/her scientific pursuits.” This is something that has always boggled my mind. As a biologist and an atheist, I have confidence in my work/study because the underlying laws of biological systems are established and follow a set of proven scientific principles. For example, when we design an antibacterial drug against a particular strain of resistent bacteria, we know for a fact that the bacteria has mutated (or evolved) and therefore the old drug doesn’t work anymore. Similarly, we use mouse, worm, and other animal models for testing compounds in vivo because we have evidence to prove that humans are genetically related to other animals through a common evolutionary ancestor. Therefore, we can study the effects of the drugs in other animals before testing them to humans. The empirical evidence that exists as the basis of our research is inherently acknowledged to be the underlying force that drives scientific research. Now, how can someone who does similar work in a laboratory setting have a completely contradictory viewpoint in his/her private life? How can someone believe in a book (or many books) that preaches blatant falsehoods about our understanding of the universe and at the same time come to work every day and do science with a conscious mind? For me, science is deeply woven into our personal lives. No, I cannot pretend that science does not affect my personal views about the world. Similarly, my conscious will never let me pretend like my personal views have no affect on my scientific work.

***

One of the most common arguments that I have come across during such discussion is that people often say “I don’t believe in *everything* that this book says. I only believe in a few things that are important for my moral framework.” This is complete BS and hypocritical. One cannot disregard a particular theory written in a book (for example, “the earth is 6000 years old”, or, “when humans die we come back as another life form on earth”), and at the same time believe in another theory written in the same book. One can’t pick and choose what you want to accept and reject from a book, and then claim the book to guide one’s moral framework.

And then there is an argument that science is not perfect and that not everything published in all of the scientific literature is true. This is absolutely correct. This is why science is constantly changing – because our understanding of the world is constantly changing. This is why scientific literature constantly undergoes modifications and updates to accommodate our latest understanding of the world and the universe.

This is not the same with religious texts. These texts were written hundreds and thousands of years ago and are obsolete in this day and age. These texts were written to accommodate the worldview of an ancient time period. They are not relevant to the 21st century and we certainly do not have to submit to these texts in order to live within a moral framework of society. As of 2017, we have discovered around 8.7 million species on earth and can estimate a hundred billion galaxies in the observable universe. We have achieved things that were once considered unfathomable by humankind. Why do we have to be stuck in the ancient past and live by some 12th century law in order to be considered as “good humans”? Of course, religious texts provide interesting insight into various philosophical questions that one can ponder over. However, they do very little to the understanding and practice of science in this day and age.

It is also often argued that we need religion to understand morality and differentiate between good and evil. Religion does not equal morality. One does not have to be a good human just to please an invisible supreme being or to go to heaven. Altruism and kindness can exist on their own.

***

Talking about scientists with personal religious beliefs, I remember a wonderful conversation between Richard Dawkins and Lawrence Krauss many years ago. I can’t help but bring up a part of their conversation while thinking about this topic –

Krauss: I’ve had people write to me and say “I’m a medical doctor and I don’t believe in evolution.”

Dawkins: That’s a disgrace. I’m not supposed to say that, especially in this country (referring to the US) because one’s private beliefs are supposed to be irrelevant. But I would walk out of a doctor’s office and not consult him anymore if I heard that he said that. Because what that doctor is saying is that he’s a scientific ignoramus and a fool.

Krauss: In fact, in that regard, it is interesting to me at the same time how people can hold beliefs which are incompatible with other beliefs they have. And in some sense, everyone is a scientist and they just don’t realize they are, and yet in the time of crisis, that’s when.. (breaks). The example I gave is when George Bush was president, he said intelligent design must be taught alongside evolution so the kids will know what the debate is all about. And it wasn’t a stupid statement at priori, it was ignorant because he didn’t realize that there’s no debate. And that’s fine. I don’t mean ignorant in a pejorative sense, I just mean he wasn’t aware.

Dawkins: Ignorance is no crime.. you just don’t want to consult a doctor who’s ignorant.

Krauss: What amazed me is that in the same administration, when the avian flu was going to be a problem and mutating to humans, president Bush said “We’ve got to find how long it takes before the avian flu will mutate into humans.” And what amazed me is that no one in the administration – not a single person said “It’s been designed to kill us, forget about it.”

Dawkins: That’s a very good point. This kind of split-brain business which you’ve been referring to, the most glaring example I know, is more in your field (referring to Theoretical Physics and Astrophysics) than mine. I was told by a professor of Astronomy at Oxford, about a colleague of his who’s an astronomer and an astrophysicist, who writes learned papers – mathematical papers, published in astronomical journals, assuming that the universe is 13.7 billion years old. But he privately believes that the universe is only 6000 years old. How can a man like that hold down a job in a university as an astrophysicist? And yet, we are told “Well, it’s his private beliefs, you mustn’t interfere with this man’s private beliefs as long as he writes competent papers in astronomical journals”.

Krauss: Well, I mean, as long as he doesn’t teach his private beliefs.

Dawkins: Well, let’s hypothetically suppose that he teaches absolutely correctly – that the universe is 13.7 billion years old. How could you want to take a class from a man who teaches one thing and believes in something that is so many orders of magnitude different?

***

About “believing” in science.

My advisor once pointed out not to use the word ‘believe’ when someone said “I believe that..” during a lab meeting presentation. Back then, I didn’t understand what was wrong in saying we “believed” in something. I now understand. As scientists, we evaluate something on the basis of observation, experiment, and evidence. The evidence is dependent on the observations made and experiments performed. Therefore, something is either likely or unlikely to occur. It is either more probable or less probable. We don’t have to believe in evolution or the big bang theory. We accept the evidence that supports them. Believing in evolution or not doesn’t make it true. The evidence for evolution suggests that it is true. Belief is not a part of rational enquiry. Belief relies on faith and not on evidence.

Does arginase mediate immune suppression in the brain?

This week I want to talk about an interesting enzyme: Arginase-I (Arg1) and its metabolic pathway in an immune microenvironment. Arg1 is a cytosolic protein that is involved in the urea cycle. Specifically, it catalyzes the hydrolysis of L-arginine to L-ornithine and urea. It has been shown that the expression of Arg1 by macrophages has an important role in tumor growth. Macrophages that are recruited into the tumor microenvironment (tumor associated macrophages) express high levels of Arg1 resulting in the depletion of arginine – an essential nutrient required for T cell metabolism. Cytotoxic T cells, therefore, can no longer function and inhibit the tumor cells from proliferating. Arg1 is implicated in several inflammatory diseases as well as in autoimmunity. Arg1 plays a significant role in mediating immune suppression and blocking its metabolism is a novel strategy in preventing tumor growth and other inflammation-related conditions.

T cell suppression by MDSC
Myeloid-Derived Suppressor Cell suppresses cytotoxic T cell function through Arg1 metabolism. (IFNγ, IL-4, and IL-13 are cytokines that induced MDSC activation)

One hypothesis is that the immune suppressive cells in other immune microenvironments in the body must be similar to the Myeloid-Derived Suppressor Cells (MDSCs) that induce T cell suppression in the cancer microenvironment. The question is, do such immunosuppressive cells express increased levels of Arg1 and act through the Arg1 metabolic pathway? Since I am interested in the brain and neurodegeneration, this hypothesis can be extended to the brain immune microenvironment. Microglial cells in the brain also upregulate Arg1 and are neuroprotective in nature (in a healthy brain). These cells are the resident macrophages of the central nervous system and function by phagocytosing cell debris and toxic misfolded proteins (that eventually form aggregates and lead to neuronal death as seen in Alzheimer’s disease) out of the brain environment. The question now is – do the microglial cells exhibit immunosuppressive behavior by altering their Arg1 metabolism?

Kan et al., 2015, recently showed that CD11c positive microglial cells are immunosuppressive in the CVN-AD mouse model and that immune suppression is caused due to the deprivation of arginine (increased levels of extracellular Arg1 causing decreased levels of total brain arginine). What isn’t explicitly mentioned in this study is that arginine is also the substrate for nitric oxide synthase (NOS) that makes nitric oxide (NO) in an alternate L-arginine metabolic pathway. L-arginine is a substrate for both Arg1 and NOS. The Arg1 pathway polarizes the macrophages to M2 phenotype and the NOS pathway polarizes the macrophages to the M1 phenotype (Rath et al., 2014). The current model of microglial activation in the CNS is limited to these two polarized states, where, the M1 microglia are neurotoxic and the M2 microglia are neuroprotective. Arg1 is upregulated in microglia in the healthy brain and aids in phagocytosis of misfolded proteins and other cell debris. The classical microglial activation is through the M2 phenotype wherein the induced nitric oxide synthase (iNOS) is upregulated thereby accelerating inflammation in the brain (neuroinflammation is one of the hallmark characteristics of several neurological diseases such as Alzheimer’s Parkinson’s, Multiple Sclerosis, Traumatic Brain Injury, etc).

M1 and M2 microglia
The current model of microglial activation is limited to the Arg1-mediated M1 and iNOS-mediated M2 polarized states.

So, if an immunosuppressive cell exists in the brain, is it possible that the immune suppression is regulated through the M2 activation and that M1 activation is absent? In other words, L-arginine is metabolized through the Arg1 pathway and not through the NOS pathway. Other questions to consider: MDSCs upregulate both Arg1 and iNOS – so how does that fit into the two-state polarization model? How does iNOS modulate MDSC activity? We know that increased NO expression by MDSCs increases T cell suppression in the tumor microenvironment. Currently, both Arg1 and iNOS inhibitors are being developed to block the immune suppressive activity of MDSCs in the cancer microenvironment. However, understanding immunosuppression in the brain is still a long way to go and the idea is not widely accepted within the neurobiology community (my understanding from the currently available literature or published studies). Investigating this mechanism in the brain will be useful in developing potential therapeutic strategies for treating neuroinflammation and neurodegeneration.

References:

  • Kan MJ, Lee JE, Wilson JG, et al. Arginine Deprivation and Immune Suppression in a Mouse Model of Alzheimer’s Disease. The Journal of Neuroscience. 2015;35(15):5969-5982. DOI:10.1523/JNEUROSCI.4668-14.2015.
  • Rath M, Müller I, et al. Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages. Front. Immunol., 27 October 2014. DOI: https://doi.org/10.3389/fimmu.2014.00532