Seeking a Cure for ALS

Rebecca Patterson '18
 

 

 

 

“Don’t ever stop learning.  Use college to learn about yourself.”

 

Aliesha Garrett ‘14, is now spending her days working at Mayo Clinic, a nonprofit worldwide leader in medical care, research and education for people from all walks of life.  The mission of Mayo Clinic is “To inspire hope and contribute to health and well-being by providing the best care to every patient through integrated clinical practice, education and research.”  Here she shares with us what it’s like working for this leader in medical care, as well as some FANTASTIC life advice.

 

Tell us more about Mayo Clinic and what you do there.
Mayo Clinic is a world class hospital system, which largely focuses on patient treatment but also sponsors its own graduate and medical school, plus some research facilities. I work at the Mayo Clinic branch in Jacksonville, FL in the research department.  While Mayo Clinic Florida also hosts an oncology research department, I work in their neuroscience program in the Petrucelli Lab (Dr. Petrucelli is the chair of the neuroscience program at Mayo Clinic Florida). My job is to maintain lab stocks and equipment, as well as perform experiments and data processing to assist graduate students, post-docs, and senior lab members with their research. I primarily work with Dr. Yongjie Zhang, and our focus is on the mechanism and treatment of Amyotrophic Lateral Sclerosis, or ALS (you may also know it as Lou Gehrig's Disease, or "that thing that people did the ice bucket challenge for").

We're primarily interested in C9ORF72, a recently discovered genetic risk factor present in ALS which proved to be the most widely distributed of any genetic link discovered so far. The five things which I specialize in at our lab are mammalian cell culture; immunostaining of human and mouse tissue and cell samples; immunoassays of cell culture and tissues; processing of human blood and tissue samples; and care, generation, behavior testing, and harvesting of a couple hundred mice at any given time, which provide a vital and novel model for ALS.

 

Are you able to incorporate your engineering background into what you do now?
Absolutely, bringing an engineering mindset into a research lab in a hospital setting provides a unique eye toward what we can accomplish with our equipment and how to approach our research questions.

 

What advice do you have for Oliners who might be pursuing a different path from engineering?
Go for it! Do whatever you are passionate about. Doing what you love can make up for a lack of experience, and people will know from your engineering degree that you're intelligent and talented.  If you have trouble getting a job in the field you really want, either form a start up or do some volunteer work on the side. Employers treat serious volunteer experience similar to work experience.

 

What is a typical day like at Mayo Clinic?
There truly isn't a typical day in the lab; we're always doing something different to keep on the cutting edge of ALS research.  In a single day we might work on half a dozen different things, from a Western Blot, an Immunoprecipitation assay, an MSD assay, creating cell lysates or tissue homogenization, behavior testing on our ALS mice, mice breeding, intracerebroventricular injections to create new model mice, generation and purification of plasmids for use in cell culture or integration into viral particles for use on mice, cell culture, cell transfection, harvest of mouse tissue, immunostaining of human or mice tissue slides or of cultured cells, generating primary cell lines, purifying DNA or RNA from a variety of sources, reading new papers in the field, writing and submitting our own papers and grants, teaching interns and graduate students, and more.

Our lab is always providing training in new protocols and techniques, with weekly seminars from researchers at other institutions, collaborations with other labs at Mayo and outside, as well as weekly internal lab meetings where our multiple investigators present their research, reach out to the group for suggestions and answers to trying questions, and bond over our achievements.

 

What do you feel you are doing that's innovative?
While our lab is at the cutting edge of research into neurodegenerative diseases, especially ALS, we use a combination of classic techniques in addition to learning and developing new approaches. Probably the most innovative thing coming out of our lab is our unique mouse model, which can be generated from any type of mouse colony rather than depending on specific breeder parents. The method of generation, intracerebroventricular injection, or ICV injection, on neonatal mice is a way to affect just the central nervous system rather than creating a systemic approach, which is typical of expression in ALS patients. The true innovation is not the injections, though, it is the viral particles which our lab designs and creates in house for use in our own labs and to ship to outside labs. Our custom adeno-associated virus, or AAV, allow us to create mice with the same genetic mutations real ALS patients have, and not only model the behavioral and physiological changes typical of ALS/FTD, but also discover mechanism and test possible treatments for ALS.

 

How have you made a difference in the world since leaving Olin?
ALS is a horrible disease, and is one of the most common neurodegenerative diseases. The disease sets in on adults, usually fairly young adults, and it handicaps them. Within 3-5 years virtually all patients die, as the muscular paralysis caused by neurodegeneration spreads to the mouth, throat, and diaphragm. In the end patients cannot eat for themselves, and most die when they are unable to continue breathing. In just 3-5 years. There are no cures, and the only treatment costs thousands of dollars a year for a mere 6 month increase in lifespan.  The research I do every day moves us forward in understanding how this happens, and moves forward testing for possible cures or preventative treatment which can mean life or death for these patients.

 

How did your time at Olin prepare you for the real world? Looking back, how did Olin help you get to where you are today?
Olin gave me great critical thinking skills, a foundation in many lab techniques, taught me how to read and write academic papers, and gave me critical experience on using teamwork to manage a long term project.  Additionally, Olin gave me my first opportunity to participate in research of my own. Working with Alisha Sarang-Sieminski was what got me interested in research as a career goal, and gave me a serious leg up on the competition for my current position. My employer loves that as an undergraduate I was able to do research and even co-author a published peer reviewed paper.

 

Do you have time for fun? What do you like to do?
Of course! Work-life balance is critical to me and my lab fully supports this. I do a lot of reading and  make regular trips to the public libraries in Jacksonville, FL. I'm also an avid gamer, both video and tabletop, and spend a lot of time playing video games, board games, and my favorite  - Dungeons and Dragons - with my friends and family. I also have a fabulous fiance, who also loves games. We plan to get married this winter (super exciting) !

Advice for current students?
Make the most of your precious time at Olin. That doesn't necessarily mean loading up on classes, although it might if that's your interest. Learn everything you can, either from joining clubs, volunteering, or just going out into the world and seeing what there is to see. Don't ever stop learning.  Also, use college to learn about yourself. Don't worry about being high achieving on paper, worry about feeling good; the rest will follow. Take care of yourself. Find out how much sleep you need. Keep your body healthy. Decide what kind of schedule makes you feel good and feel productive. Pick a hobby, or a project and give it all your love. Don't stop doing it when you graduate. Remember that you're important and you deserve to be happy.

 

 

Using a dissecting microscope to segment fetal mouse brains for primary cell culture. We can use these neurons to see the effects of genetic changes or drug treatment. Since brain biopsies aren’t a viable way to get human neurons, we either test on mouse neurons or specially engineered ‘iNeurons’. iNeurons are produced by taking human skin cells from live or recently deceased patients, forcing them to regress into pluripotent stem cells, and then driving them to differentiate into human neurons. It’s super cool.

 

 

This was my first time generating primary fibroblast cell lines! The skin biopsies came from a patient who died in the hospital and donated their tissues to our brain and tissue banking efforts at Mayo. With careful treatment and precise procedures we can make skin from a dead person grow, allowing us to continue studying their genetics to help future generations of disease carriers. The skin doesn’t even have to stay as skin; we can force the fibroblasts these biopsies produce to turn into a variety of other cell types to help us understand how mutations affect different parts of the human body, and what treatments are likely to help or hurt.

 

ALS patients and their family members generously donate samples to labs throughout the Mayo Clinic health system, so we can search for a cure. Common donations include blood, cerebrospinal fluid, and skin biopsies. From a single tube of blood like this, we can extract plasma, DNA, RNA, and lymphoblast cells. Since blood is relatively easy to draw, many ALS researchers hope we can identify definitive signs of illness, called biomarkers, in blood samples. ALS currently has no definitive test for diagnosis, and instead is diagnosed based on symptoms. Having a unique sign of disease, particularly one that is present before symptoms prevent, will be critical to identifying and treating patients in a timely and effective manner. (Plz ignore my silly facial expression)

 

A lot of times people think of albino mice and rats when they think of lab rodents. The mice I work with predominantly, though, are a strain called “C57/J B6”, a strain of dark furred lab mouse available from Jackson Laboratory. The picture here is not mine, it was pulled from the University of California Irving website, but Black Six mice are adorable, so I felt compelled to find a picture to share.

 
Posted in: Alumni Speak