primary microcephaly - College of Engineering & Computer Science

primary microcephaly

TU biochemistry professor works to uncover the causes of a debilitating neurodevelopmental disorder

woman standing in a corridor with her arms crossed while smiling and wearing a green cardigan
Assistant Professor Jyoti Iyer

Assistant Professor of Chemistry and Biochemistry Jyoti Iyer is on a quest to understand the genetic causes of autosomal recessive primary microcephaly (MCPH). This rare neurodevelopmental disorder occurs when children are born with abnormally small heads and brains.

Babies born with MCPH display several neurological defects that considerably decrease their quality of life. “Unfortunately,” remarked Jyoti, “there are no treatment options and our mechanistic understanding of how this disease is caused remains limited.”

Genetic mutations and microscopic worms

One important clue on the road to deciphering MCPH’s incidence and progression lies in scientists’ awareness that a mutation in the SAS-6 gene is associated with the incidence of MCPH in humans. Rather than studying this gene and its mutation in humans, however, Iyer is looking to C. elegans – a microscopic worm — for answers.

two women in a laboratory looking at an image on a computer monitor
Jyoti Iyer and undergraduate student Rebecca Kitchen examine an image taken using a spinning disk confocal microscope

Iyer’s research entails determining the mechanistic effects of the SAS-6(L69T) mutation in C. elegans. Her project is funded by a subcontractor award — $394,399 in direct costs and $157,760 in indirect costs — on the Oklahoma Medical Research Foundation’s (OMRF) Institutional Development Award (IDeA) Center of Biomedical Research Excellence grant from the National Institutes of Health (NIH); funding is provided by the National Institute of General Medical Sciences of the NIH under award number 5P20GM103636-09.

“Interestingly, the SAS-6 gene in humans and C. elegans is very similar,” noted Iyer. “In fact, it was first identified in C. elegans and later shown to function in much the same way in humans.” When altered, the amino acid of the SAS-6 protein causes MCPH in humans, and this mutation corresponds to SAS-6(L69T) in the worms Iyer studies.

The quest for better diagnosing, prevention and therapies

an image of part of a tapeworm produced using a high-powered microscope
C. elegans gonad exhibiting blue fluorescent protein expression in the nuclei (image acquired using a spinning disk confocal microscope)

In order to carry out this investigation, Iyer and the students assisting her in her lab used CRISPR/Cas9 genome editing to recreate the MCPH-associated SAS-6(L69T) mutation in C. elegans. The expected result of this research is the development of better diagnostic, preventative and therapeutic regimens for MCPH.

Since receiving the first installment of the award in 2021, the bulk of Iyer and her team’s work has involved characterizing the molecular and developmental effects of the SAS-6(L69T) mutation in C. elegans. During the second year of the grant, the researchers plan to submit their findings to a peer-reviewed journal for publication. They also aim to generate additional preliminary data to support an R01 proposal to the NIH.

As Iyer has gathered data during the first year and as she looks to the future, she is thankful for the “solid mentoring team” at the OMRF, comprising Linda Thompson, Dean Dawson, Wan Hee Yoon and Jian Li. “I meet with these experts on a regular basis to discuss my results and to obtain their valuable feedback on my project’s objectives and progress,” noted Iyer.

Developing and mentoring future scientists

Just as Iyer is supported by a cadre of deeply knowledgeable individuals, so too does she help to develop future scientists. In fact, all the research performed in her lab is carried out by University of Tulsa undergraduate students.

One such student, Amy Smith (BS ’21), recalled the excitement and impact of the hands-on research she was able to do in Iyer’s lab as part of the MCPH project. “My friend Mary Bergwell (BS ’21) and I were in the lab whenever we had free time to pick worms, run gels and perform experiments,” commented Smith, who now is using her education as an associate scientist with Pfizer. “Performing real skills in the lab is infinitely more valuable than learning about it in a classroom, and I am confident that if I had not been in this lab or had Dr. Iyer as a mentor, I would not be working for such a great company today.”

two women in a laboratory with the woman in the foreground using a pipette
Jyoti Iyer and her research technician Erin Haastrup

Bergwell, who today works as a research technician in the Kirkland Lab in the Department of Cell Cycle and Cancer Biology at the Oklahoma Medical Research Foundation, echoed Smith’s comments: “Gaining the hands-on experience with research in the Iyer lab imbued me with a deeper appreciation for the concepts I had learned about in my classes as a biology major. Not only was I able to fully understand the intricacies of the scientific process, I have gained invaluable insight into how research is conducted on a broader scale in addition to gaining a true mentor in Dr. Iyer and a friend in Amy. My time participating in undergraduate research in the Iyer lab has propelled me further in my career than I ever could have imagined, and for that I am extremely grateful.”

Iyer is justifiably proud of the students she has mentored in her lab. Over the past three years, for instance, Smith, Bergwell and another student, Ellie Smith, each won the Best Oral Presentation prize for their research findings at the Gulf Coast Undergraduate Research Symposium.

These and other students who have worked in Iyer’s lab have also received several internal TU awards, including from the Tulsa Undergraduate Research Challenge (TURC) and Student Research Grant Program. Several have also conducted full-time research during the summer supported by TURC and the Chemistry Summer Undergraduate Research Program.

If you want to get first-hand experience working in state-of-the-art laboratories, then you definitely need to check out the fascinating opportunities available with TU’s Department of Chemistry and Biochemistry.