What Happened to Mentoring: Offering Solutions

Marina Ramirez-Alvarado, Mayo Clinic, and a member of the Biophysical Society’s Committee for Professional Opportunities for Women, considers the state of mentoring in academia in this three part series. Read parts one and two.

We’ve already addressed the often-present disconnect between mentors and mentees that can leave students wanting, and some of the factors contributing to this situation. Today, I will talk about what can be done to improve mentor-mentee relationships.

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For mentors. Spend some time thinking about your mentoring style and history as well as your own mentors’ style and your history with them. Are you turning into your mentors the same way we turn into our parents? Do you like your mentoring style? Have you been in touch with your former students lately? Did you have fallouts with most of them and afterwards generally avoid each other at meetings? Would you join your laboratory as a student? Would you recommend yourself as a mentor to yourself as a student?

This may sound sappy but here it is: are you happy when mentoring? Are your students happy when they work with you?

Have you asked yourself why do you train students? What do you gain? What do you offer them?

For institutions. Training students should be considered a privilege and not a right. Professors should be evaluated in their role as mentors in anonymized exit interviews from graduating students. Institutions should offer continuous education options and mentoring for all faculty members that may present them with areas of improvement in their mentoring style as has been published about recently (Acad Med. 2014 May;89(5):774-82).

When a mentor/mentee relationship is established, every student and advisor should write together the expectations from both sides as a requirement to initiate research in that laboratory. Thesis advisory committees should discuss mentoring issues separately with each the mentor and mentee, to avoid conflicts of interest.

For students. Students can also contribute to reverse the rate of poor advisor/mentee matches. Senior students must be open and talk about the issues troubling them with junior students; they will make students aware of things that junior students should know so that they will be better prepared. Student support groups provide a safe environment to share and troubleshoot with peers. There is increasing evidence that these support groups can make a difference for many students by helping them avoid isolation.

Mentoring in academia is a tradition that is as individualized as each of us and simultaneously as general as the advancement of science and knowledge. Successful mentoring for all students is an undertaking that will take time and effort from everyone involved. The need is great and we should all rise to the challenge.

The author wishes to thank Dr. Estefanía Mondragón and Prof. Gabriela Popescu for their helpful suggestions to this blog.


 

Interested in becoming a mentor or mentee? Biophysical Society has partnered with the National Research Mentor Network [NRMN], an organization that matches mentors with mentees across the biomedical, behavioral, clinical, and social sciences.

Visit NRMNet to learn more and access FREE virtual mentorship, grantwriting coaching groups, mentorship training and more professional development programs and resources through the National Research Mentor Network, funded by the NIH.

 

Symmetry Principles Guide the Assembly of Protein particles

BPJ_110_3.c1.inddIn their seminal 1956 Nature paper, Francis Crick and James Watson proposed that the surface structures of viruses were produced from a limited number of protein building blocks, by using the principle of symmetric self-assembly. The ensuing years of biophysical research identified myriads of oligomeric proteins that assemble using such symmetry rules. Some proteins use polyhedral symmetry (tetrahedral, octahedral, or icosahedral) to create cage or shell-like architectures, which serve as storage, catalysis, structural scaffolding, or as enclosures for viral genomes. Our paper in the February 2 issue of BJ focuses on a de novo class of proteins, referred to as self-assembling protein nanoparticles (SAPNs). SAPNs are assembled from monomeric protein building blocks, covalently attached to antigens from pathogens, to create simple, potent, and cost-effective vaccines. The SAPN malaria vaccine candidate is currently going into the phase of clinical testing. The protein assemblies can also be modified for the delivery of functional peptides, or encapsulation of nanoparticles such as gold or quantum dots, for imaging and therapeutic uses.

The symmetric classification of different particle morphologies of SAPNs have been predicted via a mathematical formalism known as tiling theory. Reidun Twarock, a mathematical biophysicist at the University of York, pioneered the use of tiling theory in virology to solve a long-standing problem regarding the structure of the cancer-causing polyomaviridae, which exhibit more than the 12 pentagonal protein clusters expected in Donald Caspar and Aaron Klug’s classification of virus architecture.We adapted the tiling approach o model protein nanoparticles with a mixture of local 5- and 3-fold symmetry axes. In combination with electron microcopy and neutron scattering data, our classification of surface structures made it possible to identify particle morphologies that have been difficult to identify using experimental methods alone.

The cover image is an artistic interpretation of six SAPNs, five of which have been identified by the new mathematical classification. The local symmetry building blocks of the SAPNs are represented by a pentagon (5-fold axis or pentameric building block) with internal triangles (3-fold axis or trimeric building block). The middle particle, centered on the face of a pentagon, is a sixty chain oligomer which assembles according to the known icosahedral symmetry of small viruses. The other five symmetric particles, increasing in size by an order of sixty chains and centered on the vertices of a pentagon, represent extensions of tiling theory that are introduced in the paper. The nanoparticles are depicted in an aqueous solution, which takes the form of Fibonacci spirals.  The goal of the artwork is to highlight the inherent symmetry principles guiding the assembly of the protein particles, and to maintain a focus on the important role of mathematics in bio-nanotechnology. The art was created by Lauren Brunk, Annie DeGraff, Newton Wahome (adaptation of Fibonacci Pentagon by Alberto Almarza).

—Newton Wahome, Giuliana Indelicato, Philippe Ringler, Shirley A. Müller, Mu-Ping Nieh, Reidun Twarock, Peter Burkhard

Biophysics and Thyroid Conditions

January has been Thyroid Awareness Month in the US. An estimated 15 million Americans have undiagnosed thyroid problems. We recently spoke with BPS member Grace Brannigan, Rutgers University Camden, Physics Department and Center for Computational and Integrative Biology about her biophysics research related to thyroid function.

What is the connection between your research and thyroid conditions?

In most thyroid conditions, the thyroid produces too much or too little of two thyroid hormones called T3 and T4.  An initial blood test of thyroid function will usually measure thyroid-stimulating hormone (TSH), which, if out-of-range, will be followed by a measurement of T3 and T4 in the blood. One of the proteins affected by T3 is a critical inhibitory neurotransmitter receptor in the post-synaptic membrane, the GABA(A) receptor. We wanted to know if T3 could bind directly to the GABA(A) receptor, and if it could, whether the binding mode was similar to that of another class of potent endogenous small molecules called neurosteroids.  Some neurosteroids increase GABA(A) function, acting like the body’s own sedatives and anesthetics, while others decrease GABA(A) function (just as T3 does) and can improve memory and cognition.

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Why is your research important to those concerned about thyroid conditions?

There’s a well-established connection between pathological thyroid function and disrupted mood, cognition, memory, and sleep.  In fact, some studies suggest that supplementing with thyroid hormone improves mental function even in people with normal levels of thyroid hormones, although this is not established. The connection has been attributed largely to a relatively indirect mechanism in which thyroid hormones affect synaptic neurotransmitter concentrations.  Our research suggests an alternate, more direct mechanism in which thyroid hormone itself binds directly to the receptor and causes loss of function.  Further, we see that when it binds it can displace one of the endogenous sedatives, allopregnanolone, amplifying the effect.

How did you get into this area of research?

I began studying this family of neurotransmitter receptors as a postdoc at the University of Pennsylvania in the lab of Dr. Michael Klein. He had a collaboration with an anesthesiology researcher, Dr. Roderic Eckenhoff, also at Penn, seeking to understand the mechanism of anesthesia. GABA(A) receptors are one of the most widely investigated anesthetic targets and are also modulated by cholesterol-derived neurosteroids.  My research on thyroid hormones in particular began when I joined the Physics department faculty at Rutgers Camden, and began collaborating with Dr. Joseph Martin, a PI in the Biology department.  Dr. Martin has a long record of studying effects of thyroid hormone on sleep, and he and co-workers had hypothesized in the 1990s that interactions between thyroid hormones and the GABA(A) receptor could explain why too much thyroid hormone can significantly disrupt sleep.  Our joint research aims (in part) to test this hypothesis.

How long have you been working on it?

I’ve been working in the general area of ion channel pharmacology since I began my postdoc in 2006, and on mechanisms of thyroid hormones since I became a PI at Rutgers in 2011.

Do you receive public funding for this work? If so, from what agency?

The anesthesiology research that introduced me to this field was (and is) funded by an NIH PO1 grant, led by Dr. Roderic Eckenhoff.  Our research on thyroid hormone mechanisms has been funded by a three-year grant from the MCB division of NSF, soon to be up for renewal.  The computational resources provided through the NSF XSEDE program have also been critical to this work.

Have you had any surprise findings thus far? 

Maybe the most surprising findings came from Molecular Dynamics (MD) Simulations of T3 in the interfacial binding sites indicated by the experiments. These allowed us to visualize bound T3 and estimate relative affinities of pseudosymmetric sites that were indistinguishable in experiments. The GABA(A) receptor is a pentamer; It’s most commonly found as a heteromer with five similar but not identical subunits (and five pseudo-symmetric interfaces).

In the MD simulations, we found that when T3 is bound to the highest affinity interface, it can assume several distinct but equivalently favorable configurations.  One of these configurations was favorable primarily because of a hydrogen bond with the protein backbone at a well-conserved helix deformation.  These two observations suggested that T3 affinity would be relatively insensitive to most single residue substitutions.  This property may extend to other modulators, such as general anesthetics or neurosteroids, for which site-directed mutagenesis studies have yielded numerous ambiguous or inconclusive results.  The latter mystery has been primarily technical, but long-standing and a significant barrier to understanding mechanisms of GABA(A) receptor modulation.

What is particularly interesting about the work from the perspective of other researchers?

Site-directed Mutagenesis is one of the most commonly used techniques for determining ligand-binding modes.  Yet, as mentioned, it has yielded surprisingly few lasting insights for hydrophobic modulators of  GABA(A) receptors.  Structural experiments, such as x-ray crystallography and photoaffiinity labeling, are extremely time and/or resource intensive, and in some cases simply not feasible.  Our research design circumvented these issues by using an older, inexpensive technique (Schild analysis) to test for competition of thyroid hormone with one of the few hydrophobic ligands with a well-established binding site (ivermectin, determined by crystallography).

What is particularly interesting about the work from the perspective of the public?

Endocrine glands are kind of like the body’s own in-house pharmacy– they produce natural “drugs” (hormones) that can directly affect the same proteins targeted by many pharmaceuticals, even in the brain. And like pharmaceuticals that have side effects, a single hormone can act on many different systems in the body – often, especially in the brain, in ways that are still not well understood.  This means that endocrine research is naturally both basic science and health-related: the ideas and approaches developed from studying hormones can be directly applied to understanding how pharmaceuticals cause their effects and side effects – and how they can be improved.

What Happened to Mentoring: A Disconnect between Students and Advisors

Marina Ramirez-Alvarado, Mayo Clinic, and a member of the Biophysical Society’s Committee for Professional Opportunities for Women, considers the state of mentoring in academia in this three part series. 

Last week, I wrote about a disconnect between mentors and mentees that often leaves students in the cold. This week, we delve into what creates this disconnect.

Lack of communication between advisors and their mentees. The lack of communication between advisors and mentees plays a role in the problems within the swim or sink approach. In this model of training to become a scientist, you have to follow unstated secret steps to “guess” what your advisor wants because he/she is not talking to you and telling you exactly what is expected of you. In some cases, the lack of clarity about expectations happened throughout the PhD training; in others, it got lost along the way over the years. Sometimes, it just took one disagreement and the student went from being on the “good guy list” to the “evil/dumb list.”

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Differences in the way students are treated in public and in private. In this scenario, there is a disconnect between what the advisors do and say in public, during committee meetings and public seminars and what they do and say in the privacy of their offices or the laboratory. The students get a mixed message from the advisor that is very confusing and totally draining. Which message to trust? The one shared in public or in private? The positive or the negative one? For the advisor, it only takes seconds to convey a mixed message; for the student, it takes months, sometimes years to figure out what to believe, what to trust and what to do.

Advisors acquire tremendous power and control over their students. They learn what makes their students tick and use it to their full advantage. In the process, it is not uncommon that the training of the student, as well as their personal and scientific growth are not a priority.

Should I stay or should I go? dilemma. When communication between student and advisor is broken, the student receives mixed messages and the student’s training has been compromised, the student may find him/herself stuck with a project, an advisor, and a thesis project they are no longer fulfilled by. The possibility of leaving this laboratory to start again would mean getting farther behind in the training, so many students in this situation decide to stay. As a student, you are at a disadvantage by pursuing either option.

Student isolation. Many of these students are isolated and feel that they are the only ones suffering this weird treatment. No one around them is talking about these problems, so they do not feel as though they can—or should need to—reach out to anyone. Some students feel ashamed and don’t talk to anyone because they believe it would just make themselves more vulnerable to more abuse and mistreatment. What they don’t realize is that by talking to other students and in some cases, other faculty members supportive of their cause, they will begin to solve these complex issues. The simple fact that other students have similar problems and that there are faculty and students that care about them can make a difference in the life of a graduate student in trouble.

A culture of silence and lack of accountability. Students usually do not report mistreatment from their advisors, even in extreme cases where the mistreatment would qualify as harassment or abuse. They do not report because they fear retribution from the mentors, who will play a huge role in their ability to graduate and their scientific lives for years to come. They don’t report it because the graduate school education system in the US does not hold advisors accountable for bad mentoring. A future national mentoring evaluation system would allow institutions to have guidelines for best practices and accountability measures.

First year graduate students join laboratories and senior students do not feel comfortable warning them about the issues associated with their discontent. This perpetuates the trend of popular laboratories having lots of students despite bad mentoring. First year graduate students sometimes choose an advisor by following the example of other students who are doing their theses in that laboratory. What they do not realize is that each student is a unique individual and a perfect student-advisor match does not mean another student will find success with the same advisor.

Graduate students need to know that a very successful laboratory with lots of funding does not guarantee a successful PhD experience for every student.

Next time: What can be done to address these issues?

 

The author wishes to thank Dr. Estefanía Mondragón and Prof. Gabriela Popescu for their helpful suggestions on this blog series.

What Happened to Mentoring: My Views on Why It Is Sometimes Lacking

Marina Ramirez-Alvarado, Mayo Clinic, and a member of the Biophysical Society’s Committee for Professional Opportunities for Women, considers the state of mentoring in academia in this three part series.

We have all heard the horror stories, the juicy gossip shared over coffee or beer. “The mentor from hell,” “nightmare on PhD street,” “Angel in public, evil in private”… Little did I know that these stories were occurring constantly, in subtle, grayscale ways around me and causing anguish, attrition, discouragement, depression, loss of confidence, and loss of scientific human power in academia.

The word Mentor in magazine letters on a notice board

Let me start by saying that I have had great mentors throughout my academic career. None of them were perfect. We had our bad moments, but overall, my experience with them was very positive. One of my mentors lived in a different city and I only saw him one day per week, but he had set up a co-mentor for my undergraduate thesis who helped me with day-to-day issues. When I saw him, we had great conversations and he left me recharged and ready to go for the next week. Another mentor is probably one of the brightest minds in my country of origin; he allowed me to grow on my own and provided a great environment for discussion. I have never had group meetings like the ones he organized. I had a mentor who is a genius and a caring individual that taught me how to write, how to plan successful projects, and to move science forward. He also offered his help and flexibility in times of personal need. Another mentor gave me the freedom and the resources to help me become an independent scientist and showed me her way of juggling a personal life with a scientific one.

As an assistant professor, I was eager to start interacting with students, to train them, and mentor them to become better scientists than me. I got involved in as many student-related activities as I could. I joined thesis committees, I welcomed undergraduate and graduate students into my laboratory, and I taught classes. The students got to know me as an accessible, friendly professor. Let me get this straight, I am not perfect… I have had my share of bad matches with students and personnel in my laboratory. I am not the best mentor for every student. My approach when things don’t go well is to put it out on the table, talk about it, and avoid the blame game (towards the student or myself) and to learn from every experience and move on.

And that brings me to what started happening next. The graduate students from other laboratories who knew me from classes, lectures, thesis committees, word-of-mouth, etc. started coming to my office, confused, in tears, discouraged, with their self-confidence in tatters… Some of these students had started doubting every decision they were making, feeling very confused because their advisors were not supporting their efforts. They were treating these students as the worst scientists around and they were threatening them that they were never going to graduate because they were dumb. Students that normally work 12-16 hours per day were labeled as lazy when they stayed home because of a car/home repair issue or an illness. Students’ ability to perform experiments were questioned when results did not fit a mentor’s hypothesis. The students describe 180 degree changes in the attitude from the mentors that kept happening… one moment, the mentor was ‘nice and supportive,’ the other moment, the mentor was critical, cruel, mean, sometimes abusive. Some students reported receiving subtle threats, passive aggressive threats, and then straight-in-your-face threats.

Involvement in a national program focused on mentoring made me realize this these first hand stories were more than personal accounts, they were part of a national phenomenon.

I started asking myself “Why are advisors behaving this way with their students?” I realized very quickly that many of my colleagues had been “raised” in a sink-or-swim atmosphere, where they were left to their own devices. They were subjected to constant humiliation as a way to “build character” and “grow up” academically, their self-confidence attacked and their commitment to research questioned the first time they worked at a less-than-frenetic pace. I saw that my colleagues were simply “raising” their students the way they had been mentored, because in many cases, they did not know a different way.

There is a perception that to be successful you have to be utterly miserable, overworked, abused, and constantly doubting yourself. Well, let me tell you. That is not true. I live in a very different world where successful scientists care for their students and help them thrive. You do not compromise the quality of the science by treating your students in a kind way. The sink or swim system may work for certain people, but clearly does not work for all.

Over the next weeks, I will delve deeper into this issue, looking at what the disconnect is between mentors and mentees and how the problem can be solved.

Stay tuned for: What creates the disconnect between mentors and mentees?

 

The author wishes to thank Dr. Estefanía Mondragón and Prof. Gabriela Popescu for their helpful suggestions on this blog series.

Controlled electroporation of the blood-brain barrier

BPJ_110_2_3C_v2Brain endothelial cells are the major constituent of the blood-brain barrier (BBB) and permeability is the key to successful drug delivery across the BBB. The BBB regulates the transport of different substances from blood to the brain by moving through the cell (transcellular transport) or between the cells (paracellular transport). However, it is considered an obstacle to efficient delivery of drugs that target the central nervous system.

Pulsed electric fields are one of several methods that have the potential to temporarily make the BBB permeable when substances are traveling through the transcellular or paracellular pathways.  The electroporation phenomenon is mainly responsible for opening the cell membrane and enhancing the transcellular pathway across the BBB. Therefore, in order to get a more accurate picture of this transport phenomenon, it is necessary to investigate the effect of electropermeabilization on the endothelial cell monolayer of the BBB.

For transcellular transport to occur, molecules are first absorbed through the apical side of the cell membrane into the cytoplasm, and then they pass through to the basolateral side. Therefore, monitoring cellular absorbtion provides insight into possible enhancement of transcellular transport for different substances and can help us determine whether or not a certain treatment is effective in transporting drugs across the BBB.

The cover image shows the permeabilization of the brain endothelial cell monolayer at different sections of the tapered microfluidic channel, which is implemented in this study as a platform for delivering the pulsed electric fields. The electric pulses were applied at the channel ends, making a gradient of electric field across the channel which is inversely proportional to the channel width. Therefore the electropermeabilization could be monitored for a range of electric field magnitudes in a single experiment. The cells were initially stained in green using calcein AM and then pulsed in the presence of propidium iodide (PI), which is naturally impermeable to the cells. Upon entering the cell, PI stains the cell nuclei red, making it a valid probe for monitoring absorption. The images are taken using an inverted fluorescent microscope with two filters which enable the visualization of red and green stains.

The results from varying pulse strengths and the number of applied pulses may provide information that can be used to find the proper parameters to enhance transcellular transport across the BBB using pulsed electric fields without causing any permanent damage.

– Mohammad Bonakdar, Elisa Wasson, Yong Woo Lee and Rafael Davalos

How Do I Prepare My Poster? How Do I Give a Talk?

Sections of this article are adapted from the article “Do’s and Don’ts of Poster Presentation,” by Steven M. Block, published in Biophysical Journal, Volume 71, December 1996.

Congratulations! Your abstract has been accepted for the 60th Annual Meeting of the Biophysical Society and your poster has been scheduled in with thousands of others during the meeting. What do you do next? How do you prepare for the presentation? What can you do to stand out from the others? Even if this is not your first presentation, it is important to keep certain things in mind while preparing your poster and presentation.

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First, consider how your poster will look—the size, colors, font, and flow of it. Think of your audience—people walking through the poster hall, glancing around for interesting topics. Most important on your poster is the title. The title of your poster does not need to match the title of your abstract. In fact, it’s best that it doesn’t. Your abstract title is probably long, incredibly descriptive, and possibly laden with jargon. But you are trying to attract people to come over and read your poster, so keep the title short, snappy, and to the point. Make sure someone can get a general idea of your topic just from reading the title – and make sure they can read the font from a reasonable distance.

Once you’ve lured readers to your poster, you want to make sure they can actually read the text you’ve so painstakingly put together. Fonts smaller than 12-point are just too small for a poster—14-point should be used as a benchmark for the absolute minimum font size (think fine print), and the main text should be 18-20 point or larger (the title should be even bigger). If your text doesn’t fit at that size, consider editing your text, not decreasing the font size. While we’re talking about fonts, keep in mind that poster presentations are not the right place to experiment with fun, fancy fonts (save those for e-cards to your Nobel Prize celebration!). Use fonts that are easy to read. If you want to move from the traditional Times New Roman, stick with something equally basic, such as Baskerville Old Face, Century Schoolbook, or Palatino Linotype. Make sure whatever font you choose works well with any equations or symbols you use. Once you’ve selected a font, keep your choice (and size) consistent throughout the poster.

You may want to draw readers to you by making your poster a bright color, or adding patterns or some other loud visual cue. There’s nothing wrong with a little color in your poster, but keep it professional (avoid neon hues, unless they’re relevant to your research), and keep it readable by making sure the colors contrast well—if you want a navy blue background, your font color should not be deep magenta.

Now that you’ve settled on the basic font, size, and color choices, it’s time to lay out your poster. Break your presentation into logical sections that easily flow from one to another, to help your reader follow your research. Start in the top left, moving vertically first, then left to right. Make sure to include any additional authors towards the beginning of your poster and any relevant references towards the end—it is very important to give credit to everyone involved!

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With your poster finished, it’s time to prepare your actual presentation. You’ll want to stick around near your poster for as much time as you can to engage with readers, answer questions, and of course meet and network with other scientists interested in your research. Definitely plan to camp out by your poster for at least the hour that you are scheduled to present. Keeping in mind that most people will only stop for a moment, and even those who linger will only do so for three to five minutes, put together an “elevator speech” with the top points you want to make and practice it! To help develop your presentation, test it out on a colleague or labmate to get feedback on your clarity and delivery.

Engage curious parties in conversation, but be careful to not badger anyone, or to be too engrossed in any one conversation (thus ignoring everyone else). You can always schedule a follow-up with very interested individuals if needed. If you have them, bring business cards (or paper and pen) to share your contact information with anyone interested in follow-up.

If you come prepared with a well-designed poster, a few key talking points, and copies of any necessary ancillary materials, you can hang your poster and then let your science speak for itself!