As a part of our Microbiome Awards winners interview series, we spoke with Marsha Wibowo of Harvard Medical School, who will carry out her project at the Joslin Diabetes Center. Ms. Wibowo is the winner of the PhD Student category of the 2018 Microbiome Awards. Her project will examine the role of extinction events in the gut microbiome in promotion of obesity and type 2 diabetes (T2D). We interviewed Ms. Wibowo to discuss her current research and future plans.
How did you first get interested in science and microbiome research?
Since I was in high school, knowing how so many of my friends and family members were affected by diabetes, I was determined to study biology and contribute to the field of diabetes [research]. My dreams came closer to reality when I received undergraduate admissions to MIT, where I majored in Biology and had the opportunity to do research for four years. Coming to Harvard for my graduate studies, I was convinced to pursue diabetes research. To my surprise, I learned for the first time from Dr. Aleksandar Kostic’s talk about the gut microbiome, how much is unknown, and its correlation with diabetes. I was excited to discover more about how the gut microbiome can impact T2D progression and treatment, which led me to join Dr. Aleksandar Kostic’s Lab and Dr. Yu-Hua Tseng’s Lab.
Can you give a summary of your project submitted for the Microbiome Awards?
Obesity and diabetes have become an epidemic; 36.5% U.S. adults are considered obese and the number of Americans with diabetes has increased almost 3-fold in the past 15 years, and this trend is predicted to continue to rise. In addition to genetics and lifestyle, evidence has shown that the gut microbiome might contribute to T2D development. Mouse studies have shown that feeding mice with a high-fat diet over multiple generations leads to compounding diabetes phenotypes across generations, but the mechanisms remains elusive. This study aims to determine whether Western diet causes compounding loss of healthy gut bacterial species that leads to worsening of diabetes phenotypes across generations. If this holds true, we aim to test whether reintroduction of these lost bacteria, in addition to lifestyle changes, is required to improve obesity and diabetes. To test whether Western diet results in losses in the gut microbiome over multiple generations, we will feed mice with a high-fat diet for 4 generations. We will compare the gut microbiome of the mice across generations and assess the host diabetes characteristics, such as body weight, blood sugar level, and insulin level. We predict that across generations, mice will lose bacterial species and show more severe diabetes characteristics. To test whether reintroduction of these lost bacteria is required to improve obesity and diabetes, we will test whether fecal transfer, in addition to dietary changes, can improve obesity and diabetes to a larger extent than dietary changes alone.
What will be a typical day for you in the lab?
A typical day for me includes both wet lab and computational work. From the wet lab side, I work with mice to collect fecal samples or characterize their metabolic phenotypes. I extract DNA from fecal samples and build sequencing libraries for shotgun metagenomic sequencing. Computationally, I spend time analyzing my metagenomic data.
What do you find most interesting about your project? What is the most interesting or surprising result you have found?
Since we are following the microbiome and the host longitudinally for four generations, there is much we can learn from the data, especially to identify novel microbiome-host interactions as the host develops diabetes. This might enable us to develop new treatments by targeting the microbiome. One interesting preliminary result we have seen is how the diabetes phenotypes compound across generations in our mouse cohort. We are still waiting for the metagenomic data, and I am looking forward to dissecting the microbiome-host interactions using this dataset.
What kind of microbiome research do you perform and how does it impact health and disease or the environment? Where do you see this heading in the next five years?
I study whether diet-induced extinction events in the gut microbiome contribute to diabetes progression. If our hypothesis holds true, dietary and lifestyle changes alone might not be enough to slow the increasing rate of diabetes epidemic. Introduction of lost bacteria might be the key to making significant improvements in obesity and diabetes treatments. In this study, we hope to find gut bacterial species that are important for improving obesity and diabetes and introduce these bacteria into patients as a treatment. In the next five years, I hope we can restore our microbial diversity and re-introduce lost bacteria into humans to prevent or treat diabetes.
What are your hobbies?
I use a great deal of my free time for volunteer work, mentoring younger students to organize and carry out service projects. I also like traveling, dancing, and enjoying various forms of arts, including paintings, sculptures, and spoken word poetry.
What are the major challenges you face in your research with regards to sample collection, nucleic acid isolation and data analysis?
For sample collection, sometimes it is difficult to get the quantity of fecal samples that we need from the mice. We also need to make sure to minimize contamination and store the samples properly. Challenges with nucleic acid isolation and library preparation include minimizing contamination and making sure the protocols and reagents are standardized across all samples. For data analysis, there are many software [packages] and tools available, so we need to choose the best and most cost-efficient ones for our data analysis.
Which QIAGEN products do you use/have you used in the past and what did you like about the products?
We have used the QIAGEN DNeasy PowerSoil Kits for DNA extraction. I like the product because it is easy to use, has clear instructions, and the entire protocol is quite fast. The quality of our metagenomic sequencing data from using this kit is good.
What was your reaction when you found out you were a finalist in the Microbiome Awards?
I was very thrilled and quite surprised. I am sure there were a lot of qualified applicants, so I am honored to be a finalist. I am excited because if I win the award, I would be able to sequence many samples and generate a lot of interesting data!