A day in the life — graduate student and genomics researcher Neha Bokil

Graduate student Neha Bokil moves around the Page lab with urgency. Today, she’s running an experiment using white blood cells from patients with varying numbers of X and Y chromosomes.

The lab of Whitehead Institute Member David Page investigates the role of the X and Y chromosomes beyond determining sex. While most females have two X chromosomes (XX) and most males have one X and one Y chromosome (XY), there are individuals whose sex chromosome constitution varies from this, having instead, for example, XXY, XXX, or XXXXY. With the goal of understanding why certain conditions are more prevalent in one sex versus than the other, Bokil is using this experiment to explore if and how cellular processes, such as gene regulation, vary among individuals with these atypical combinations of sex chromosomes.

Partially hidden in the cell culture hood, Bokil finally locates what she's been searching for: a pipette for dispensing 99 microliters of the cell suspension she’s meticulously prepared this afternoon, a type of culture where cells float in nutrient-rich liquid, free to function and grow.

Bokil carefully extracts this volume and transfers it to a flat plate — also called a 96-well plate — with tiny holes for growing small cell samples. Now, it’s a waiting game until she can find out how these cells are growing, and whether their proliferation rate depends on the number of sex chromosomes in a cell.

Bokil dives into the intricacies of human genetics every day, hoping her work will eventually help reshape how sex differences are understood in medicine and improve treatment outcomes. The dynamic research Bokil is conducting at Whitehead Institute is her calling, but she has other passions as well. Here’s what a typical day in her life as a graduate student looks like, both in and outside the lab.

An inherited love of numbers

When she isn’t rushing out the door, Bokil loves brewing and savoring the perfect cup of morning chai, a traditional South Asian loose-leaf tea with milk. Every family has their own recipe, and Bokil makes hers with ginger, a touch of cardamom, and some sugar.

“Chai is comforting at any time, but I’ve noticed my mood vastly improves when I’m able to have a cup in the morning,” she says.

On her walk to the Whitehead Institute, she often listens to Bollywood songs. But these predilections — chai and Indian cinema — are more than just rituals for her. They symbolize tradition and cherished connections with family and friends.

In fact, family bonds have greatly influenced Bokil’s career path. As a child, she loved mathematics. It wasn’t a trait passed on genetically, but one that flourished through moments of connection with her grandmother, a math teacher in India. During summer visits to Bokil’s family in the U.S., she’d enthusiastically impart her passion for numbers onto her granddaughter. By the time Bokil went to high school and later college, she had become fluent in the language of logic and patterns.   

“My time with her made me realize just how beautiful and fun math is, and I could see its practical applications in everyday life, all around me,” Bokil says.

For her PhD, she sought to combine her undergraduate training in mathematics and molecular biology to tackle a real-world problem. With genetics at the crossroads of these disciplines, and the Page Lab leading the way in transforming scientific understanding of X and Y chromosomes beyond reproduction, Bokil knew she had to get involved.   

This morning, as she sits at her desk, poring over a research paper before an afternoon lab meeting, she ponders how insights from the study could enhance her manuscript writing process. Bokil’s graduate project uses a collection of cell lines derived from patients with atypical numbers of X and Y chromosomes to investigate mechanisms that regulate — or dial up and down the expression of — genes located on one of the X chromosomes in females called the “inactive” X chromosome.  

Although the X and Y sex chromosomes in mammals began as a pair with similar structures, over time, the Y chromosome underwent degeneration, leading to the loss of numerous active genes. In contrast, the X chromosome preserved its original genes and even gained new ones. To maintain balance in gene expression across the two sexes — XX and XY — an evolutionary mechanism called X chromosome inactivation emerged.

This process is known to randomly silence one X chromosome in each XX pair, ensuring that both sexes have an equal dosage of genes from the X chromosome. However, in recent years, the Page lab has discovered that there are powerful distinctions within females’ pair of X chromosomes, and the so-called “inactive” X chromosome is far from passive. Instead, it plays a crucial role in regulating gene expression on the active X chromosome.

“That’s not all,” adds Bokil. “There are still genes expressed from that “inactive” X chromosome. Cracking how these genes are regulated could answer longstanding questions about sex differences in health.”

Bokil is unraveling this genetic mystery with the help of chemical tags called histone marks. These tags cling to a family of proteins that function like spools, allowing long strands of DNA to coil around them — like thread around a bobbin — so genetic information remains neatly packaged within the cell’s nucleus.   

This complex of DNA, RNA, and proteins is called chromatin, the genetic material that eventually forms chromosomes. Chromatin also lays the groundwork for gene regulation by keeping some genes tightly wound around the histones, rendering them inaccessible, and unwinding others for active use.

Certain histone marks are associated with open chromatin structure and active gene expression, while others indicate closed chromatin structure and gene silencing. By examining the specific histone marks on proteins near genes on the “inactive” X chromosome, Bokil aims to decipher if and how these genes are turned on and off.

She’s particularly interested in a group of genes that have counterparts on the Y chromosome. These genes, known as homologous X-Y gene pairs, are typically dosage-sensitive and play a crucial role in regulating essential processes throughout the body like the transcription of DNA into RNA and the translation of RNA into proteins.

Celebrating small triumphs

Graduate school can feel like a marathon — progress is slow but every small step counts towards a breakthrough. For Bokil, stumbling upon a captivating scientific puzzle has been a stroke of luck she deeply appreciates. In fact, the mystery of how genes are controlled on the “inactive” X chromosome has not only shaped her scientific pursuits but also her artwork — on one quiet evening at home, she found herself inspired to capture an experiment, called CUT&RUN, in her painting.

During the early days of her PhD, Bokil spent hundreds of hours using this technique to identify the precise locations of histone protein and DNA interactions. Right as she was prepared to expand these experiments across multiple cell lines, the COVID-19 hit, throwing her plans — and progress — off course.  

During these challenging times, Bokil found solace in her cultural roots and the warmth of community. She began teaching virtual BollyX classes — a dance similar to Zumba, but on Bollywood tunes — every Tuesday evening as a means to stay connected, a commitment she’s upheld ever since throughout her time in graduate school.  

Beyond nurturing a sense of togetherness through dance, Bokil is committed to mentoring in science and celebrating improbable victories along a tedious research journey.

“I had a former lab mate who used to do what she called a data dance every time she had a graph she felt happy with,” Bokil recalls. “I think that should catch on a little bit more because it’s always a really good feeling to see how these experiments that have taken up so much of your time and effort are leading somewhere.”