The Experience of Research as an Undergrad

Ah, research! Cutting-edge technology, exciting chemicals, pushing the limits of knowledge with your own two hands! But is that all there is to it?

The reality is that pushing the limits of knowledge requires a lot of inspiration, and takes a really freaking long time. Doing research is not your run-of-the-mill undergraduate lab. There, you do one experiment, say, synthesize aspirin, which has already been well characterized and done numerous times by a vast number of people You then you write about your specific attempt and all is well and good. In research, you don’t have the luxury of previous renditions of the same experiment because they’ve already been done, so what’s the point?

Instead, you need to find a new topic to study so that you can appease: 1) your supervisor, 2) your advisory panel, and 3) a funding agency, if you get there. Each of these require a more original and “exciting” experiment, and often those are quite hard to find. In fact, losing your research topic because someone else has already studied it, Usually, people tend to find new topics by looking into similar topics and tweaking them slightly, or delving deeper into a topic that has only been generally covered. This involves reading A LOT of papers so that you can become an expert on the current status of the research area you’re interested in. Also, keep in mind that while you will have help along the way, ultimately you must decide on the topic on your own because it is YOUR project, not your supervisor’s; otherwise, what’s the point?

Finally, after digging through trawls of papers, you have solidified your research topic and you are pretty confident that it will be exciting enough to give you a degree (let’s not get ahead of ourselves to the grant stage yet). However, since your topic is so new and exciting, you have no idea how you’re going to do it or if it will even work. You can ask around for help from people in your surroundings, but odds are they are not familiar enough with your topic. After all, you chose this topic specifically because it is new, and nobody has really researched it yet. So how do you proceed? By, guess what, reading more papers! In this case reading papers is like an extension of asking people in your surroundings. You won’t get the exact answer you’re looking for, but you can get an approximation of what you can do to get results. Also, thanks to modern technology, there are now internet resources such as research gate to help you in addition to reading a ton of papers, so all is not lost.

After much scrounging around, you are finally ready to plunge into research, exciting! Time to collect data!

…but collecting significant data also takes a long time and along the way you will inevitably have experiments that fail, reagents that degrade, part of your project getting scooped, etc. Eventually, you will succeed in enough experiments to get data to write a thesis and get your graduate degree, but if you plan on pursuing academia look forward to having to do this all again for your PhD! And then your post-doc! And maybe another post-doc! And then if a university accepts you into their faculty, your assistant professorship, which is like a more intense post-doc! And at the very end of the road, when you are finally offered tenure, you’ll realize that the things you have been doing this whole time are the same things you’ll be doing from now on as well: reading papers, creating experiment proposals, reading more papers, doing experiments, etc. This is also why professors always seem so old – getting to that stage takes a long time.

All this may sound really daunting and maybe even discouraging, but this is just a run-through of the drier parts of research. When you’re knee-deep in some sprawling experiment (and they always become sprawling), it’ll seem like there is never enough time. When your experiment fails and you have to read more papers, you’ll learn cool things you didn’t know even from all your previous education. You’ll meet people who will be experts about things you’ve never even heard about. You’ll get to use cutting-edge technologies and exciting chemicals just like you thought you would. And, at the end, when your experiments do succeed and you have collected enough data on top of all the knowledge you have amassed during the process, you will really have discovered something that nobody has ever seen before and nobody yet knows about, until YOU tell them about it! Now tell me that isn’t the coolest thing ever. (You really can’t.) The long path of research definitely has many downer moments and dry patches, but it is equally full of excitement and discovery. As long as you have patience and are undaunted by occasional failures, you truly will be on the frontline of pushing the boundaries of human knowledge.

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Evidence that New Doctors Cause Increase in Mortality Rate in the UK

In England, there is a commonly held belief that it is unsafe to be admitted to the hospital on “Black Wednesday”, the first Wednesday of August. Each year, this is the day when the group of newly certified doctors begin working in National Health Services (NHS) hospitals. One study compared the likelihood of death for patients who are admitted in the final Wednesday of July, with patients who were admitted in the first Wednesday in August. This study found that there is a 6% higher mortality rate for patients who are admitted on Black Wednesday.

There are 1600 hospitals and specialist care centres that operate under the NHS. Each centre routinely collects administrative data when admitting their patients. A group did a retrospective study using the archived hospital admissions data from 2000 to 2008. Each year, over 14 million records are collected. Two cohorts of patients were tracked: one group being patients who were admitted as emergency—unplanned and non-elective patients in the last Wednesday of July. The second cohort comprised of patients who were admitted as emergency patients in the first Wednesday of August. Patients who were transferred were taken into consideration to avoid double counting.

Each cohort was then tracked for one week. If the patient had not died by the following Tuesday, they were considered alive. Otherwise, if they had passed away by the following Tuesday, it was counted as a death. The study only tracked patients for one week, because it was deemed to be the best method to “capture errors caused by failure of training or inadequate supervision”, on the part of the junior doctors. Having a short-term study also avoided any possible biases that may arise from seasonal effects that would complicate the analyses.

The study only analyzed emergency admissions to ensure randomness in the data. They wanted to avoid bias that could have resulted from differences in planned admissions due to administrative pressures.

After considering both cohorts, the study analyzed 299741 hospital admissions, with 151844 admissions in the last week of July, and 147897 in the first week of August. They found that there were 4409 deaths in total, with 2182 deaths in the last week of July, and the last week of August.

The study found small, non-significant differences in the crude odds ratio of death between the two cohorts. However, after adjusting for the year, gender, age group, socio-economic deprivation, and co-morbidity of the patients, it was found that patients who were admitted on Black Wednesday had a 6% higher risk of mortality. The 95% confidence interval ranged from 1.00 to 1.15, and the p value was 1.05.

In short, for hospitals in the NHS from 2000 to 2008, it was found that there was a small, but still statistically significant, increase in the risk of death for patients who were admitted on Black Wednesday, over patients who were admitted the week prior.

 

Source: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007103

Sustainable Farming (feat. Rocks!)

Climate change is one of this generation’s most persistent and pressing problems. It not only affects sea levels, habitats, and wildlife, but also resources vital to human survival. One of theses resources is food: as we deplete fertile land, waste fresh water, and cause severe weather changes, we increase the risk of our global food security.

The rapid growth of the human population means that food security will soon become a concern for both developing and developed countries alike. To address this issue, Dr. David J. Beerling and his colleagues from the University of Sheffield are researching agricultural practices that not only preserve the environment, but also act to undo human pollution. In a paper published by Nature on 17 January 2018, the team put forth a farming practice that uses silicate rocks to remove carbon dioxide from the atmospheres.

The process involves the regular addition of small pieces of calcium and magnesium-bearing rocks into the soil. The silicate rocks react with the carbon dioxide in the atmosphere to form stable alkaline forms of carbon dioxide (namely bicarbonate and carbonate), then carry the compounds with the rest of the soil runoff into the ocean. This process therefore assists with the reduction of carbon dioxide in the atmosphere (a major cause of Earth’s severe climate change).

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Image courtesy of Nature

Dr. Beerling’s research also indicates that his team’s process improves crop performance, and can act as a substitute for fertilizers. The silicate rocks can also increase the pest and disease protection of the crop. Dr. Beerling hopes that the benefits will create an incentive for farmers to adopt the practice.

Of course, there are financial and practicality issues preventing this novel process from being adopted. For instance, a substantial amount of silicate rocks is required to accomplish the carbon sequestration (or removal of carbon dioxide from the atmosphere). For 10 to 30 tonnes of carbon dioxide per hectare of crop per year, 9-27 pentagrams of silicate rock is needed. Moreover, a cost-effective way to obtain these rocks does not exist either. Our current rock mining, grinding, and spreading technologies would likely yield carbon emissions equivalent to 10-30% of the carbon that would be sequestered by the silicate rocks obtained. The research paper consequently emphasizes the need for innovation in the industrial sector in sustainable rock mining practices.

Finally, because this idea is so novel, further research and greater public acceptance is needed for it to become common practice. If effective, however, silicate rocks have the potential to reshape sustainable agricultural practices.

Resources

https://www.nature.com/articles/s41477-018-0108-y

Alcohol and Potential DNA Damage

A recent study completed by the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge suggests a novel reason for why alcohol consumption increases the risk of cancer. In a study published in Nature on 3 January 2018, the Cancer Research UK-funded experiment found that alcohol consumption causes DNA damage in stem cells. In particular, the DNA of haematopoietic stem cells (blood stem cells) are adversely affected by alcohol consumption.

Previous studies that have investigated the carcinogenic effects of alcohol used cell cultures for their experiments. The experiment conducted by the MRC laboratory adopted a novel approach and exposed live mice instead of cultures to ethanol. After chromosome analysis and DNA sequencing of the mice’s genetic information, the team noticed permanent chromosome alterations in the blood stem cells. In particular, the acetaldehyde produced by the body upon consuming alcohol breaks the double-stranded DNA and causes chromosome rearrangements. These mutations increase the risk of cancer because the stem cells become faulty.

The MRC laboratory experiment also observed the role of the enzyme aldehyde dehydrogenase (ALDH) in the body’s response to alcohol. They noticed that mice lacking a functioning ALDH enzyme had four times as much DNA damage as those who did. This confirms our understanding that ALDH is one way the body mitigates the effects of alcohol; ALDH converts acetaldehyde into acetate, which the body uses as energy.

The insight into ALDH’s function in the body compliments our current understanding of the enzyme. For example, a large portion of South East Asians, who on average have lower alcohol tolerances, lack functional versions of ALDH enzymes. This study may also suggest that, based off of one’s inherited ability to produce ALDH enzymes, some individuals may be more prone to the carcinogenic effects of alcohol than others.

Lastly, the study did recognize that cells have DNA repair systems. However, not everyone carries a seamless DNA repair system, as they can often be lost due to chance mutations. Further, with substantial enough alcohol exposure, these systems may fail (as they did with the mice) and result in DNA damage.

The study did not conclude whether such DNA damage was hereditary, as the lab only looked at blood stem cells. Nevertheless, Cancer Research UK has publicized this study as a compelling reason to control alcohol intake and consume in moderation.

Resources

https://www.nature.com/articles/nature25154

https://www.sciencedaily.com/releases/2018/01/180103132629.htm

Not Sure About SURE?

McGill’s Summer Undergraduate Research in Engineering (SURE) Award gives undergraduate students a 16-week, full-time internship position at an engineering research lab at McGill. Awarded as a scholarship, recipients receive an endowment valued at a minimum of $5,625 and the opportunity to work at a lab for the summer.

The 2018 SURE Application period opened on 16 January, initiated by an information session held on the same day. This year, the Faculty of Engineering is offering 125 awards: a substantial jump from the 90 offered last year. The decade-old program is funded by the NSERC Undergraduate Summer Research Award Program, the Faculty of Engineering, the Trottier Institute for Sustainable Engineering and Design, and other donors.

Overview

The “summer research traineeships” provide students with exposure to research and the graduate school experience. For the first time ever, SURE will also be recognized with an entry on students’ transcripts.

SURE participants work on one of the many research projects associated with the program. The research projects for 2018 were posted on the Faculty of Engineering website on 16 January. There are projects from the Departments of Architecture, Bioengineering, Chemical Engineering, Civil Engineering, Electrical and Computer Engineering, Mechanical Engineering, Mining and Materials Engineering, and Urban Planning. Each project has an associated professor, and some require a minimum study year.

Application Process

Interested students need to contact the supervising professors of the projects they are interested in, to a maximum of 3 projects. Supervisors must first agree that the student should apply to the project before the student can complete the Online Student Application.

Once the student has filled out the application, they will submit it to their selected supervisor. The deadline to apply is 26 January 2018, and the first round of awards will be announced after 19 February.

If you would like more information about SURE, or to access its application, please visit the Faculty of Engineering’s website here.

Soup and Science: Bringing students close to the research

Feature Photo: From McGill University’s Facebook Page

In the beginning of each semester, the Faculty of Science organizes Soup and Science, a week where professors in different departments discuss their current research. Each day features four or five professors, in fields such as (but definitely not limited to) biochemistry, mathematics, management, psychology, and geography. Each professor is given the opportunity to summarize their research in three minutes.

This is an opportunity for undergraduate students, specifically those in U0 and U1, to understand what “research in a research-intensive university is all about”. Listening to talks on the cutting-edge research conducted at McGill allows students to bridge the link between the foundational information they learn in classes with research and the future of their respective fields.

This semester, Soup and Science is running from January 15 – 19 at 11:30-12:30 every day at the Redpath museum. Students should come early, since spaces fill up quickly.

On Wednesday, January 17th, Suzanne Fortier, the President of McGill University, was a special guest to this series of mini-talks. The talks opened up with the perspective of a student, followed by five McGill professors, and concluded with a series of questions about the talks. After the presentations, students are offered free soup and sandwiches.

Sasha McDowell (Final year Honours Biology student)

Sasha McDowell is an international student who is strongly interested in understanding more about her field. In her second year at McGill, she began working in a molecular biology laboratory during the school year. After taking BIOL 306, Neural Basis of Behaviour, she found herself so interested in the course topic that she began working in the Watt Lab on a SURE scholarship over the summer. In these sixteen weeks of work, she worked with mice and tested potential therapies of human ataxia diseases. Wanting to gain insight into all the aspects of research, she took a field course where work was conducted Mont. Saint-Hilaire. McDowell described the value she found in discovering all the avenues that research consists of.

Professor Nii Addy (Desautels Faculty of Management)

Professor Nii Addy completed an undergraduate degree in Engineering before beginning his work in Management. His work focuses in the cross-sector partnership between different organizations to solve complex societal problems. He showed the group an example of a complex problem; the increase of obesity rates among US adults from 1990 to 2006. In order to solve this systemic problem, it is important to consider a “multiplicity of perspectives”. He described the impact of minor changes, such as proximity, on major changes, the commonplace of obesity in North America. Professor Addy currently works with a “multidimensional proximity framework” to help solve complex societal issues.

Professor Kevin Manaugh (Dept. of Geography, McGill School of Environment, Associate of the School of Urban Planning)

Professor Manaugh’s work primarily deals with the design of sustainable cities. He showed the group images of cities before city-planning became a profession, in which industry were situated next to homes, child labour was prevalent, and cities were commonly plagued with societal, economic, and environmental problems. Ebenezer Howard blazed the trail for urban planning when wrote a book on the idea of a garden city, where cities were designed with the concept of “separation of uses”. In fact, most of North America has developed around this idea of a garden city. Dr. Manaugh’s work deals with how to best design the urban environment in a way that reduces the environmental impact, increases biodiversity, and includes the voices of marginalized people. In his own words, the vision of his research is to improve human well-being while making cities more resilient, socially inclusive, and having less environmental impact.

Professor Eric McCalla (Dept. of Chemistry)

Dr. McCalla is a new professor at McGill who researches in advanced batteries. He described the usefulness of lithium-ion batteries in our mobile devices and electric vehicles. However, the current state of research has not yet allowed these batteries to be utilized in renewable energy. For this to be done, the lifetime of the batteries need to be increased five fold, and the batteries need a higher energy density. In his lab, Professor McCalla studies the effects of different compositions for the positive electrode, and is hoping to study the possibility of replacing the current, liquid electrolyte, with a more stable solid electrolyte.

Professor Thibault Mesplède (Dept. of Microbiology and Immunology)

Dr. Mesplède’s lab currently study HIV, a virus that is not cured by antiretroviral therapy. He hopes to discover whether viral reservoirs are latent, or persistently replicating in hidden spaces or anatomical sites, much in the way that microbial organisms can be found within the extreme conditions of hot springs or freezing tundra. His lab uses deep sequencing to reconstruct viral evolution and the phylogeny of HIV.

Professor Jackie Vogel (Dept. of Biology, Associate professor in Computer Science)

By training, Dr. Vogel is a chemist and a biologist. However, her lab is truly interdisciplinary, using techniques from mathematics and computer science to mine data from biological systems. She currently focuses on the “gaps of knowledge that are particularly interesting”. More specifically, she wishes to find the mechanism that occurs from prophase to prometaphase in mitosis. Spindle pole bodies need to be perfectly aligned along a certain axis in order to replicate properly. She uses a basic projection from linear algebra to determine whether or not the cells have aligned their spindles. By studying a mutant that fails to do so, she is currently working on quantitatively analyzing and visualizing this step in mitosis.

Research Awareness Day 2017

November 25th, 2017 marked the annual Research Awareness Day (RAD) held by the Biochemistry Undergraduate Society (BUGS). One of the most prominent undergraduate research events of the year with over 80 undergraduate attendees, RAD featured a full day of rapid-fire presentations by 10 different biochemistry professors, lunch, and a poster fair featuring graduate and undergraduate students alike. With the diversity in the research topics of the different professors, there was something for everybody, not just those majoring in biochemistry.

Once again, RAD 2017 was a great event to learn more about research, network with profs, and to get excited about science. You definitely do not want to miss out on RAD if you have the chance, but for those that didn’t make it to RAD 2017, here’s a glimpse at what the professors talked about:

Dr. Albert Berghuis

As the chair of the biochemistry department, Dr. Berghuis gave a brief snapshot of biochemistry at McGill, past (biochemistry is one of the oldest departments at McGill!) and present, before presenting his lab and his current research. The Berghuis lab centers around structural biology and drugs: the development of anti-cancer drugs, the identification of fungal drug targets, and various other drug related topics. But no topic is as pressing as the central feature of the Berghuis lab: antibiotic resistance. Taking a structural biology approach, using techniques such as x-ray diffraction, NMR, scattering, and electron microscopy, the lab seeks to use structures of bacterial enzymes that confer antibiotic resistance to develop new, better antibiotics.

Dr. Jose Teodoro

The Teodoro lab is in equal parts biochemistry and virology, as their primary focus is to learn how to kill cancer cells using viruses that only seem to kill cancer cells by honing in on specific cellular features that only cancer cells possess. For example, the chicken anaemia virus, which causes anaemia in chickens, only targets and kills rapidly dividing cells by interacting with the Anaphase Promoting Complex/Cyclosome. While this destroys chicken hematopoietic stem cells, it is fantastic news for cancer biologists since cancer cells also tend to divide rapidly. Furthermore,the chicken anaemia virus is small, and its only function is to target and destroy rapidly dividing cells. The Teodoro lab also works on p53, a very well known gene that encodes a tumour-suppressing transcription factor, and its effects on tumor angiogenesis.

Dr. Ian Watson

The Watson lab focuses on melanocyte biology in melanoma. 50% of melanomas have a hotspot mutation BRAF, and 25% have a hotspot mutation in NRAS, both of which are mitogen-activated protein kinase (MAPK) regulators, and are druggable targets. The goal of the lab is to develop a therapeutic strategy for long-term survival, as many current techniques show initial promise but no increase in the rates of long-term survival. The Watson lab created stable Cas9-encoding mice with which genome manipulation can be easily done, and they also collect samples from patients who underwent checkpoint inhibition therapy, so they have excellent models for melanoma, the poster child for precision therapy of the future.

Dr. Alba Guarné

One of the newest additions to the McGill biochemistry department, hailing from McMaster University, the Guarné lab studies genome stability and DNA-protein interactions. DNA needs to be extremely condensed to fit into the tiny nucleus of the cell. Almost all DNA processes require the DNA to be decondensed. Once this occurs, the DNA is under constant attack by many components of the cell. Over time, this constant attack can lead to significant mutations in the DNA if it weren’t for the DNA repair mechanisms that prevented the accumulation of mutations. One of the projects the Guarné lab is currently undertaking is the analysis of DNA mismatch repair, specifically studying how the mechanism can discern which of the two DNA strands contain the mutation. All this is done through structural biological techniques such as x-ray diffraction and EM microscopy.

Dr. Janusz Rak

The Rak lab, at the Montreal Children’s Hospital, is a cancer and angiogenesis laboratory, asking questions related to the complexities of diseases. One disease the Rak lab studies specifically is glioblastoma, a type of brain cancer that kills nearly 100% of patients due to the tendency for the tumour to hemorrhage in the brain, and its peculiar penchant of forming blood clots elsewhere, such as the leg, demonstrating the interactivity of cancer. The lab is interested in the unconventionally connectivities of cells — one that does not involve neither the neural nor the endocrine system. Glioblastoma cells exemplify this lack of convention as they seem to communicate using extracellular vesicles, which Dr. Rak described as “motherships that can change things in different ways”. Techniques used in Dr. Rak’s lab include atomic force microscopy and liquid biopsy.

Dr. Uri David Akavia

The Akavia lab is interested in metabolism bioinformatics in cancer, conducting computer modelling of the metabolism of the entire cell, specifically in cancer cells. The lab also intentionally changes genes known to be involved in metabolism using Cas9, and observes and models the consequences. (This leads to some pretty wild flow charts). Ultimately, the Akavia lab seeks to examine how cancer metabolism makes the cell resistant to treatment or developing cancer, and to develop treatment options from the results.

Dr. Bhushan Nagar

The Nagar lab uses structural biology techniques, specifically x-ray crystallography, to decipher molecular mechanisms that underlie diseases. The lab has a diverse range of research interests, such as analysis of IFIT proteins, members of the innate immunity which interact with viral RNAs to block their replication; AvrA, a bacterial protein that blocks immune signalling in the host cell to promote successful infection by the bacteria; and lysosomal enzymes, a subset of acid hydrolases whose mutations lead to lysosomal storage diseases. The Nagar lab hopes to use information gleaned through structural analysis to develop better therapeutics, such as drugs and pharmaceutical chaperones, for associated diseases.

Dr. Alain Nepveu

The ultimate goal of the Nepveu lab is to develop a novel cancer treatment by exploiting vulnerabilities of the cell (not JUST rapid divisions, but other characteristics as well), as well as examining base excision repair. The Nepveu lab uses mouse models and a lot of different assays to collect the data. Dr. Nepveu also stressed the importance of starting research early, and that you don’t need to have prior research experience to conduct interesting experiments in the lab — the skills you learn from making pizza at your part-time job can be transferred to running a PCR! But ultimately, you should not be shy to approach professors to ask about getting research experience.

Dr. Jason Young

The Young lab’s primary focus is on chaperones, specifically the Hsp70s and 90s, which anyone can learn about in GREAT detail if they take BIOC 212/ANAT 212 from the man himself, but Dr. Young’s RAD presentation was about how to get involved in research, in which he also stressed that you don’t need research experience to get involved in research at the undergraduate level, and that there are many classes such as the 396s and independent research courses available to students, providing a helpful and resourceful end to the rapid-fire talks.