Author Archives: Parham Asli

Studying DNA has never been easier…Thanks to eVITTA!

There’s one thing that every single one of us has in common with each other and all other living beings. It’s the fact that we carry DNA in our cells. DNA is an important molecule that has all the inherited information about how a living thing will look and function. A strand of DNA is like an extremely long sentence that uses only four letters – in fact, the length of the human DNA is 600 billion letters long! Can you imagine how hard and time consuming it would be to read? That is why scientists at The University of British Columbia (UBC) have developed a new and exciting application called easy Visualization and Inference Toolbox for Transcriptome Analysis, or eVITTA for short. eVITTA simplifies analyzing RNA (a type of DNA) and not only makes the process more efficient, but improves scientists’ understanding of its information as well.

The kind of DNA information that eVITTA works with is called the “transcriptome”. The transcriptome is the full set of RNA, which are the copies of DNA, within a cell. Analyzing the information in the transcriptome is crucial; for the past few decades, it has been one of the most used techniques for investigating diseases and their mechanisms.

The analysis of transcriptome data, however, is very tedious and time consuming. You have to retrieve the data, examine it, and then compare it with other transcriptome datasets to draw a conclusion. This involves several steps and different types of programs, which can be inefficient. eVITTA was created to combine the many steps of transcriptome analysis into one simple, user-friendly interface. This speeds up the process of transcriptome analysis immensely!

The tedious process of analyzing long strands of DNA is simplified with eVITTA.
Image Credit: CI Photos/Shutterstock.com

evitta was born out of excess data!

One of the many topics that sparked our interest was understanding the circumstances surrounding the creation of eVITTA. As Dr. Yan of UBC’s Taubert Lab puts it:

This whole project was born out of our need to pass on data. We have a lot of transcriptome data from past years that no one has gotten around to analyzing…. so during the pandemic, we started digging into those data and developing visualization modules and we realized we can actually make this into an app so that we can feed more data and generate visualizations

The team behind eVITTA

To discuss the different aspects of eVITTA and to delve deeper into this project, UBC’s Shayan Abbaszadeh sat down for a virtual interview with PhD candidate Judith Yan from the department of Cell and Developmental Biology at UBC. Dr. Yan is one of the many faces behind eVITTA at the Taubert lab and has worked tirelessly to bring this idea into fruition. Our podcast describes her role in realizing the gaps in efficient transcriptome analysis and building eVITTA with the rest of the Taubert Lab during the COVID-19 pandemic. Outside of eVITTA, Dr. Yan’s lab work in the Taubert Lab usually involves using model organisms such as roundworms to study stress responses and applying that knowledge to better understand human diseases. 

How does eVITTA make analyzing RNA so simple?

To grasp the scope of this research, first and foremost, it is important to understand transcriptome analysis. Dr. Yan describes transcriptome analysis as a powerful tool that examines how RNA, a copy of DNA, is used in a cell, tissue or organism. This involves taking out the whole RNA from a sample, getting it sequenced (i.e. decoded), and subsequently obtaining information from that data.

An exploration of gene patterns is one of the main aspects involved in effective transcriptome analysis.  A gene is a section of DNA that carries a specific piece of information. A crucial aspect of analysis is understanding that some genes are turned on at higher rates than others. According to Dr. Yan, once there is a count for these different genes, the numbers can be interpreted to reveal useful information about “what some of these genes are doing” and “what processes and gene sets are actually being changed“. Finally, there needs to be effective visualization techniques of the different data sets and the data needs to be validated against previously published data. 

All of these functions are achieved through eVITTA; a user-friendly, web-based interface that streamlines the multiple steps of transcriptome profiling. Watch this short video to become familiar with the 3 modules of eVIITA; easy-GEO, easyGSEA, and easyVizR, and realize what effective transcriptome analysis looks like!

The challenges of transcriptome analysis and how evitta addresses them

In our podcast, we focused extensively on the motivations behind the creation of eVITTA, specifically in relation to challenges associated with transcriptome analysis and how eVITTA deals with these challenges in ways that previous methods could not. Dr. Yan alludes to the use of the ‘overrepresentation approach’ (ORA) in previous technologies that has the flaw of only being able to represent a small subset of gene changes. As Dr. Yan puts it: “you’re missing out  on a lot of information and biologically… you are not able to capture the less severe changes. eVITTA on the other hand, focuses on entire sets of genes instead of just one gene, allowing scientists to observe gene changes across the board. 

Additionally, previous technologies did not allow for the organization of data because “oftentimes it is very tedious to do multiple comparison because you have many different subsections that you want to look at“. eVITTA prevents the dumping and mislabeling of gene data which expedites the process of discovering important biological patterns. This platform has already been proven to be highly effective in studies involving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and roundworms (C.elegans). 

Dr. Yan’s research using eVITTA involves the starvation response of C.elegans roundworms. (credit: Taubert lab)

what does the future hold for eVITTA?

Our podcast also discusses the future of eVITTA and the team’s plans for further expansion. Dr. Yan and her team plan to add more algorithms to analyze the expression of different genes at a more in-depth level. The team also want to add more visualization options to provide more choice for gene dataset analysis. Finally, they are planning to update eVITTA’s databases by adding more datasets to the application. These ideas and more are discussed in our podcast below!

As transcriptome profiling provides major insight regarding diseases and illnesses, the optimization eVITTA can provide may be increasingly vital for today’s society. For instance, if transcriptome analysis can be conducted more efficiently, crucial findings in disease mechanisms may be discovered sooner. As a result, treatments and health regulations can be created more quickly, potentially saving lives and preventing disease spread. Additionally, eVITTA’s user-friendly and web-based interface makes transcriptome profiling accessible to more biologists around the world and would therefore greatly benefit the research community.

– Heather Cathcart, Kaushali Ghosh, Parham Asli, Shayan Abbaszadeh

 

 

 

The future of male birth control is within reach!

Now here’s something you may not know… condoms are over 5000 years old! That’s right, some of the first forms of birth control date back to thousands of years ago, and while the condom has made huge strides in the millennia that have passed since then, the only other option that exists for men in birth control is a vasectomy that may be hard and often costly to reverse. Well, that is until recently! A new scientific breakthrough has allowed scientists in The United States to design a male contraceptive pill that is 99% effective in preventing pregnancies in mice and is awaiting human trials!

there is a significant discrepancy in the contraceptive options available to women as opposed to men, signaling the need for more balance. Getty Images/Peter Dazeley

How does it work?

The male body needs a certain nutrient called retinoic acid, a form of vitamin A, for fertility, sperm formation and sexual drive. The male contraceptive pill, which was first unveiled at the 2022 American Chemical Society’s spring meeting a few days ago, is equipped with certain compounds that block crucial proteins from binding to retinoic acid receptors (RAR), hence allowing for reliable and reversible sterility in male subjects. The compound was administered orally to mice for a 4-week period. Not only did the compound result in a dramatic decrease in the mice’s sperm count, it also had no observable side effects. Better yet, once they stopped administering the drug, the mice regained the ability to give birth in 4-6 weeks!

In order to minimize potential side effects, the chemicals within the drug were designed such that they would specifically bind to RAR. This way, surrounding tissues will not be affected. But more importantly, the chemists and pharmacologists responsible for developing this drug at The University of Minnesota, attribute its success to the fact that it is completely non-hormonal!

The pill targets Vitamin A and has been shown to cause sterility in male mice. Getty Images/Canopy

what makes a non-hormonal pill better?

Up until now, there have been numerous attempts to create a male contraceptive pill, but any compound that has thus far reached the clinical trial stage, exclusively targets the male sex hormone testosterone. Unfortunately, this may  be accompanied with a slew of side effects including increased cholesterol levels, weight gain, depression, and increased risk of cardiovascular disease. This is why current efforts have been targeted towards the non-hormonal pathway to developing a male contraceptive pill.

When can the world expect to see the pill?

Clinical trials are set to begin by the end of 2022. The researchers behind the pill have teamed up with a private company, YourChoice Therapeutics, to achieve this goal. While there is actually no guarantee that the pill will replicate the same results in humans, there is a high level of optimism that the pill can be marketed to the general public in 5 years or under. Jesse Mills, director of the men’s clinic at UCLA jokes “It’s hard to ask a mouse about moodiness or fatigue or other side effects that may manifest in human studies”. Nonetheless, the current pill offers more promise than previous options.

Research associates at The University of Minnesota announce that the pill is ready to begin clinical trials in 2022. CTV News

 

The tiny but mighty solution to antibiotic resistance

So picture this… It’s the year 1928 and penicillin has just been discovered. Penicillin revolutionized modern medicine and with other antibiotics to come, it would go on to treat the untreatable and save millions of lives. Now, let’s flash forward to a more grim version of the future. It’s the year 2022. Antibiotics were supposed to be our precious resource but every time we misused them or overused them, we gave bacteria a chance to evolve and become resistant, and at the same time our scientists were unable to bring new antibiotics to the market. The World Health Organization (WHO) is calling antibiotic resistance “one of the biggest threats to global health today” so in recent years scientists have been looking for new multi-dimensional strategies to combat this issue. One of those is the use of light-activated quantum dots.

Over-prescription and patient non-compliance exacerbate the issue of antibiotic resistance. Getty Images/Joe Raedle

What are quantum dots?

Quantum dots are tiny particles made of semiconducting material, meaning they partly conduct electrical current. They are only a few nanometres in size and can be engineered in terms of shape, size, and material. The way these quantum dots kill bacteria is not all that complicated. Basically, when our bodies are infected with bacteria, they naturally produce what scientists call Reactive Oxygen Species (ROS) in our immune cells to kill bacteria, and what light-activated quantum dots do is that they essentially mimic this natural killing process of the body by producing ROS of their own.

How is the killing initiated?

Now you may be thinking, how do we ensure that the cells that are not infected with bacteria, don’t end up getting killed? Well, the answer is quite simple. In application, quantum dots are specifically injected at the site of bacterial infection in the human body, so as to not affect other tissues, and when they receive an input of light of sufficient energy in a process called photoactivation, their electrons (particles with a negative charge of electricity) jump from a region of space with lower energy called the valence band to a region of space with higher energy called the conduction band. The energy difference between these two is referred to as the “bandgap” and when the electrons relax back to their ground level (i.e. the valence band), a photon of light is released that provides the energy needed for producing the killer Reactive Oxygen Species.

An input of light causes electrons of the quantum dots to move around, energy is released, and the killer ROS come to life! Adapted from Redox-Active Therapeutics

What are the consequences?

The killer ROS will break down bacterial biofilms (self-contained bacterial communities), damage the bacterial cell wall and cell membrane and inactivate enzymes needed for bacterial survival. And because the ROS are killing these microbes through all these different non-specific ways, the microbes can no longer develop resistance!

Quantum Dots and their many ways of killing bacteria! Adapted from McCollum et
al. and Imlay

One for the future?

It is abundantly clear that quantum dot technology shows great promise in combating the widespread issue of antibiotic resistance. Although the clinical use of the technology is a long way off, the strategy is an intriguing new approach at a time when the rate of drug development is much slower than the rate of antibiotic development and the pharmaceutical industry is lagging behind.

Student research on the applications of quantum dots at The University of Colorado. Materials Research Society