In efforts to help researchers produce quality medicine worldwide, Northeastern’sBiopharmaceutical Analysis Training Laboratory, established in 2014 and directed by Jared Auclair, is training students, researchers, and drug regulators worldwide on the best practices and challenges involved in producing new drugs. In early 2019, Auclair’s lab received a $4.3 million grant from the Massachusetts Life Sciences Center to expand its research space, which is being used to help trainees understand potential issues in the drug-making process, such as falsified data or information that has been tampered with, Auclair says.

Associate teaching professor of biotechnology, Jared Auclair, says as the scientific community rushes to develop a vaccine and treatments for the COVID-19 illness, the quality and safety of new drugs is more important than ever.

This article was originally published on News@Northeastern on May 5, 2020. To read more, click here.

Dr. Ali Wallace ’13 works as a Pediatric Resident Physician at Massachusetts General Hospital. She took time out of her increasingly busy schedule to give us an inside look at COVID-19 preparations, as well as to discuss how her experience at Northeastern shaped her into the doctor she is today.

Can you tell me about your experience at Northeastern?

I started my journey at Northeastern as a Chemistry major. I quickly realized the lab environment wasn’t for me (thanks co-op!) so transitioned into Biochemistry, with a minor in Psychology.

I lived on campus for a majority of college, which I absolutely loved (don’t ever take for granted those floor-to-ceiling-window-Boston-views in West Village).

I also did a Dialogue Program abroad in Italy. I spent my free time dancing in a few club groups (first season of No Limits Dance Crew!) and going on hikes with NUHOC, which I will forever be grateful for because that is how I met my now husband!

I graduated in 2013 and miss college all the time!

What kind of co-ops did you go on?

My first co-op was doing Immunology research at Biogen – a pharmaceutical company in Cambridge. I worked with cell lines and mice, and learned a ton, but mostly that I wasn’t cut out for an entire career in a lab.

I knew I wanted to work with people and I found a more clinical co-op as a Newborn Hearing Screener at Brigham and Women’s Hospital, which I still believe to be the best job ever! I cuddled newborns all day and got to congratulate new parents when their baby passed its “first test”! This was my first clinical experience in Pediatrics and it obviously left an impression on me. I really enjoyed the Pediatricians I worked with, the hospital environment, and being a part of special moments on a daily basis.

How did Northeastern and COS help shape your interests and/or prepare you for what you’re doing today?

I am forever grateful for the flexibility that Northeastern gave me while trying to find my ideal career path.

I came to college passionate about Genetics, inspired by my older sister who is developmentally disabled. I just didn’t quite know what that looked like in terms of a future career. You’ll never know if you like something until you try it!

I always loved science, but never really considered clinical medicine until after I realized I didn’t want to work in a lab. I always wonder where I would have ended up if I didn’t have that first co-op experience early in my college career. But every experience along the way has helped me to learn more about myself and the things that kept me going each day.

Where did you land after you left the University?

I was lucky enough to be accepted to Tufts University School of Medicine – right down the road from NU! I was one of 5 fellow Huskies in my class, which was awesome! Medical school was an awesome experience, and my time at Northeastern definitely prepared me for the trials and tribulations of life as a med student.

You’re currently at MGH as a Pediatric Resident Physician. What’s a normal day look like for you?

Yes! I am currently in my third and last year, and will be graduating in June! Every day is truly different and unpredictable.

We rotate through various parts of the hospital (Emergency Room, PICU, newborn nursery, NICU etc) and with various sub-specialties (Oncology, Cardiology, Pulmonary, etc) so each block is very different and your role is ever-changing.

This makes life as a resident exciting, but also stressful. We work days, nights, weekends, and 24 hours shifts. On a typical day on an inpatient unit (just to give you a rough idea), we get sign out from the overnight team at around 6:30 am.

We have lectures around 8 am, and spend the morning rounding, or going room to room to see each patient. The team usually consists of a senior resident, and intern, and a couple of medical students. We examine our patients, make a treatment plan, talk with families, and order any tests or labs that are needed.

The afternoons are for learning, following up on results, and admitting new kids to the hospital! There are rarely dull moments. I see sick children in the Emergency one day, and well children in clinic the next! I love attending deliveries of newborns – my favorite thing ever is showing a brand new dad how to cut the umbilical cord. The various reactions and responses are priceless!

Do you find the work rewarding?

I may be bias, but it is hard for me to imagine anything more fun or rewarding than taking care of children.

They are incredibly resilient, wise, and loving. We dress up for holidays at work, partake in crafts, birthday parties, and last day of chemo celebrations.

The work is hard, but there aren’t many days when I’m not smiling. My co-residents are also amazing, and I like to think that Pediatricians in particular are just nice and genuine people- one of the biggest things that drew me to the field in the first place!

With the COVID-19 outbreak, can you talk about your current role is and how work at MGH has evolved over the past couple weeks?

What an unprecedented time.

Today is March 16^th, and I know things will be much different 1 week from now. MGH is full of incredibly smart and hard working people who having been working endless hours to keep our community safe, and I am honored to be part of such an institution.

Life as a resident has changed dramatically – all elective rotations or roles that are not necessary have been cancelled. We have actually been cutting back on the number of residents in the hospital to limit potential exposures amongst staff. Many of us are at home on back-up call, practicing social distancing and staying healthy until we will have to replace others that become sick.

We have continued having educational conferences virtually, while supporting those on the front lines until we get called in to work.

Based on some recent research, children are less severely affected by the virus, so our department is prepared to help out on the adult side when necessary. There has been a lot of careful preparation for whatever the next few days/weeks throw at us.

Is there anything you’re not hearing discussed enough when it comes to the outbreak that could help people be proactive and stay safe?

I encourage people to visit the CDC website for the most up to date information, as recommendations have been changing by the hour.

But I will say, this is not a time to be cavalier about the coronavirus. While you may not feel at risk as a young, healthy, college student, the downstream effects of transmission are extremely frightening.

We need to prevent the collapse of our medical system and every decision you make counts. Wash your hands, stay home if you are sick, and don’t hang out with large groups of people.

Help each other out! Grab groceries for an elderly neighbor; offer to pick up things for friends if making a trip to the store.

And finally, stay connected with friends and families virtually! These are trying times, and we can all use each other’s support. Keep an eye out for virtual concerts (ie Dropkick Murphy’s St. Patrick Day show, or the MET Opera, who will be streaming shows for free!) and free yoga and exercise classes that can be done from home.

The number of products advertised as containing CBD, a compound derived from cannabis plants, has skyrocketed. Consumers can purchase CBD-infused burgers, coffee, beer, and toothpaste, as well as creams and oils marketed as treatments for pain, anxiety, and even cancer.

But what, if anything, do these products do? And are they safe? And do they even contain CBD? The research into these questions is scant.

Now, researchers at Northeastern University and Loyalist College in Ontario, Canada are teaming up to train graduate students in the analytical techniques required to investigate cannabis, and help them understand the regulatory landscape in both Canada and the U.S. The partnership also plans to create a robust research enterprise surrounding cannabis and other areas of biotechnology.

Jared Auclair directs Northeastern’s biotechnology programs, as well as the Biopharmaceutical Analysis Training Laboratory on Northeastern’s Burlington, Massachusetts campus in the U.S. Photo by Adam Glanzman/Northeastern University

“There’s not much research or data that says adding CBD has any clinical effect—it’s all anecdotal,” says Jared Auclair, an associate teaching professor of chemistry and chemical biology at Northeastern, who is leading Northeastern’s side of the partnership. “This is a research opportunity for our students to apply what they learn to a scientific question that happens to focus around cannabis.”

The new partnership won’t focus solely on CBD. The researchers and their students will be evaluating all aspects of cannabis, including potential medical uses and the psychoactive component of recreational marijuana known as THC.

While marijuana remains an illegal substance at the federal level in the United States, 11 states and the District of Columbia allow it to be used recreationally, and 33 states have legalized it for medical use. In Canada, recreational use was legalized in 2018, and researchers at Loyalist were studying medical marijuana even earlier. That, combined with Loyalist’s proximity to Northeastern’s Toronto campus, makes the school an ideal partner for this project.

“Cannabis is legal in all of Canada, and Loyalist is an active player in researching CBD, THC, and other aspects of cannabis,” says Auclair, who directs Northeastern’s biotechnology programs, as well as the Biopharmaceutical Analysis Training Laboratory on Northeastern’s Burlington, Massachusetts campus in the U.S., which provides people from around the world with training in the manufacturing practices and regulatory considerations necessary to bring pharmaceutical products to the market.

“This is an opportunity for us to have joint classes, joint workshops, and other programs around cannabis, but also around the biotech industry in general,” he said.

When the country legalized recreational marijuana, new opportunities opened up to work with the burgeoning industry. Loyalist was the first college in Canada approved to study cannabis,  and launched Canada’s first post-graduate certificate program in cannabis applied science in 2018.

What, if anything, do CBD products do? And are they safe? And do they even contain CBD? The research into these questions is scant. Photos by Matthew Modoono/Northeastern University

“This has provided support for us, as an academic institution, to work with industries that are focused on the scientific basis for their product development,” says Kari Kramp, who is the principal investigator for Loyalist’s Applied Research Centre for Natural Products and Medical Cannabis. “To better understand the plant, and to better understand the process in which they grow the plant, the ways in which they analyze the plant, and how to generate innovative, high-quality, consistent products for the market.”

Students from Loyalist have already taken a course at Northeastern’s Toronto campus examining international regulations surrounding cannabis, and Auclair traveled to Loyalist’s campus to speak to biotechnology students about opportunities in the field.

The new educational and training programs for graduate students at both institutions will officially begin this summer, and joint research projects will start in the fall. Auclair is also working with his Northeastern colleagues to add opportunities for undergraduates in the future.

As the partnership grows, both Auclair and Kramp stress the importance of providing students with training and experience to set them up for success after they graduate. Northeastern has an existing global network of thousands of co-op employers and Auclair anticipates that Loyalist’s network of industry partners will offer new co-op opportunities for students in Canada, specifically. Additionally, students will be able to practice valuable analytical techniques as they investigate new cannabis products, and their findings could provide key insights for consumers and regulators.

“They’ll have the opportunity to put to use some of the skills that they’ve learned,” Auclair says. “And also interact with the regulatory environment in Canada.”

Photo by Matthew Modoono/Northeastern University

Currently, regulatory agencies have only a small handful of scientific studies to base their cannabis decisions on. The United States Federal Drug Administration has approved only one CBD-based drug, which helps treat patients with rare, severe forms of epilepsy, and recently issued a statement that other CBD products may not be safe and certainly aren’t legal. But the World Health Organization released a report in 2018 that said CBD generally seemed safe and wasn’t associated with any public health problems.

Meanwhile, the U.S. Congress passed a bill in 2018 reclassifying hemp, a strain of the cannabis plant which contains high levels of CBD and very low levels of THC, as an ordinary agricultural crop instead of a controlled substance. As a result, the production of hemp has more than quadrupled, the CBD industry has exploded, and regulatory agencies are scrambling to keep up.

In addition to serving the students of both schools, this partnership will provide an avenue to tackle some of the unanswered questions around cannabis and provide concrete evidence for future regulations.

“For these policymakers, for governments, for regulators, to make informed decisions, more research needs to be done,” Kramp says. “I think that’s the bottom line—more information is a good thing.”

This story was originally published on News@Northeastern on January 8, 2020

Researchers at Northeastern have discovered a new antibiotic that could treat infections caused by some of the nastiest superbugs humanity is facing in the antibiotic resistance crisis.
After two years of work, a team of researchers led by Kim Lewis, University Distinguished Professor of biology, announced their discovery of darobactin, which can kill resistant microbes known as gram-negative bacteria.
The discovery, published today in Nature, promises to be a much-needed weapon in the war on drug-resistant bacteria, which are estimated to cause 700,000 deaths each year worldwide.

“We are running out of antibiotics,” says Lewis, who directs the Antimicrobial Discovery Center, where the discovery of darobactin was made. “We need to be looking for novel compounds with no pre-existing resistance in the clinic or the population.”

Yu Imai, a postdoctoral research associate in Lewis’ lab, discovered the compound from Photorhabdus bacteria that live inside the gut of a nematode, a tiny parasitic worm found in soil. It’s the first time, Lewis says, that the animal microbiome was found to harbor an antibiotic that promises to be useful for humans.
In experiments using mice conducted by Kirsten Meyer, also a postdoctoral research associate in Lewis’ lab, darobactin cured E. coli and Klebsiella pneumoniae infections, with no signs of toxicity.

The newly discovered compound breathes new life into the search for a solution to the antimicrobial resistance crisis. The molecule has a unique structure and an unusual mode of action that make it particularly effective against gram-negative bacteria.

“We have never seen anything remotely similar to that before among antibiotics,” Lewis says.

Gram-negative bacteria, which include E. coli and Salmonella, have an additional, outer membrane that shields them from many types of antibiotics. This extra protection is why gram-negative bacteria are at the top of a list of “priority” pathogens that need to be targeted with new antibiotics, compiled by the World Health Organization.
Bacteria can also acquire additional resistance mechanisms from other microorganisms, which can make them largely impervious to currently available antibiotics. In a process biologists call horizontal gene transmission, bacteria pick up DNA from the environment and incorporate it into their genomes. These new genes can then be passed down to future generations.
This ability to pick and choose DNA is also how Photorhabdus bacteria, which have been around for hundreds of millions of years, acquired the genes coding for darobactin, Lewis says.

“What were they doing for the last 370 million years?” Lewis says. “I think these bacteria screened the entire biosphere for antibiotics of use to us.”

Nematodes and Photorhabdus bacteria have a symbiotic relationship that helps them prey on different kinds of insects, such as caterpillars. Inside a caterpillar, nematodes release Photorhabdus bacteria, which in turn release toxins that kill the caterpillar and turn it into dinner.
But as the symbionts dine, the Photorhabdus also have to fend off freeloaders from the environment, which might also want to feast on the dead caterpillar. These opportunistic microbes can come from the nematode’s own gut, which happens to be full of the same gram-negative bacteria that attack humans.

“Since Photorhabdus bacteria live in the nematode, and the nematode is an animal just like we are, whatever they make has to be non-toxic [for us],” Lewis says. “These compounds also have to move through and survive in the tissues of the caterpillar, which is also an animal and is actually very similar to us.”

More than 50 years have passed since the introduction of the last class of antibiotics that target gram-negative bacteria.
The restrictive outer membrane of gram-negative bacteria is built with the help of an essential protein that sits on the surface of the cell. This protein, called BamA, works like a gumball machine that opens and closes a gate to dispense chewing gum. In these bacteria, BamA opens and closes a gate periodically, taking in freshly made proteins and inserting them into the protective membrane. That open-and-close mechanism is the vulnerability of these bacteria, Lewis says.

“Darobactin binds to that [BamA] protein and jams it, so it cannot open anymore,” he says. “The bacteria cannot build a proper cell envelope, and that causes death.”

When Lewis’ team tested E. coli that had developed resistance to darobactin, the bacteria lost their ability to infect mice. That means gram-negative bacteria cannot change the BamA protein without losing their ability to infect.
Eric Brown, Distinguished University Professor of biochemistry and biomedical sciences at McMaster University in Hamilton, Ontario, says the discovery of darobactin is an example of research “from soup to nuts” in terms of finding a compound from natural sources, figuring out a target, doing animal studies, and sorting out the way the organism makes that compound.

“They didn’t set out to find the BamA inhibitor, they just kind of stumbled on it,” Brown says. “It’s just kind of a master class on how to find a unique natural product antibiotic.”

This story was originally published on News@Northeastern on November 20, 2019.