my research in molecular biology

In addition to my photography, I take pride in my contributions to science. For those interested, I have provided a brief overview of my past research, along with links to my publications.

During my time as a Master’s, doctoral, and postdoctoral researcher in the Lourido Lab at MIT, I studied the human parasite Toxoplasma gondii. About a quarter of the world’s population is chronically infected with this parasite, yet we still lack treatments to eliminate Toxoplasma from those affected. It is a leading cause of foodborne illness, often spread through contaminated food, particularly meat, as well as through contact with cat feces and mother-to-child transmission during pregnancy. While usually harmless, Toxoplasma can cause severe disease in unborn children and those with compromised immune systems, making it a significant global health concern. Current strategies for controlling the disease focus primarily on preventing transmission, underscoring the need for new treatments.

Developing effective treatments for Toxoplasma requires a deeper understanding of its biology at the molecular level. However, many of the necessary tools for such investigations are either limited or nonexistent. To address this, I adapted advanced gene-editing techniques—specifically CRISPR—for use in Toxoplasma. CRISPR, renowned for its versatility and ease of use, has revolutionized research in various organisms, and its application has significantly expanded our understanding of Toxoplasma biology. By leveraging these techniques, we are now better equipped to identify the parasite’s vulnerabilities, paving the way for new therapeutic approaches.

One of the key outcomes of my research was the creation of a genome-wide map of Toxoplasma promoters—DNA sequences that regulate gene activity. This map, covering approximately 7,000 promoters, facilitates the use of powerful research tools, including CRISPR interference, a technique I adapted to selectively control gene expression. By targeting specific genes, we can investigate their function and evaluate their potential as therapeutic targets. Together, the promoter map and CRISPR interference significantly enhance our ability to study Toxoplasma and accelerate the development of new antiparasitic drugs.

The data I generated and the findings I made are serving as valuable resources for parasitologists worldwide, advancing current and future projects aimed at elucidating Toxoplasma biology and mapping new pathways toward antiparasitic therapies.

1. Markus BM, Boydston EA, Lourido S. CRISPR-mediated transcriptional repression in Toxoplasma gondii. mSphere (2021).

2. Markus BM, Waldman BS, Lorenzi HA, Lourido S. High-resolution mapping of transcription initiation in the asexual stages of Toxoplasma gondii. Frontiers in Cellular and Infection Microbiology (2021).

3. Wang Y, Sangaré LO, Paredes-Santos TC, Hassan MA, Krishnamurthy S, Furuta AM, Markus BM, Lourido S, Saeij JPJ. Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages. Nature Communications (2020).

4. Harding CR, Sidik SM, Petrova B, Gnädig NF, Okombo J, Herneisen AL, Ward KE, Markus BM, Boydston EA, Fidock DA, Lourido S. Genetic screens reveal a central role for heme metabolism in artemisinin susceptibility. Nature Communications (2020).

5. Herneisen AL, Sidik SM, Markus BM, Drewry DH, Zuercher WJ, Lourido S. Identifying the target of an antiparasitic compound in Toxoplasma using thermal proteome profiling. ACS Chemical Biology (2020).

6. Markus BM, Bell GW, Lorenzi HA, Lourido S. Optimizing systems for Cas9 expression in Toxoplasma gondii. mSphere (2019).

7. Ingram JR*, Knockenhauer KE*, Markus BM*, Mandelbaum J, Ramek A, Shan Y, Shaw DE, Schwartz TU, Ploegh HL, Lourido S. Allosteric activation of apicomplexan calcium-dependent protein kinases. Proceedings of the National Academy of Sciences of the United States of America (2015).

The cover image shows a composite of data visualizations from my publication on transcription initiation in Toxoplasma. The image is centered horizontally on the dominant transcription start sites of ~7,000 Toxoplasma genes and shows a range of coordinates extending 500 basepairs in up- and downstream directions. The purple histogram shows the per-basepair average activity of transcription initiation on the sense (values extending upwards from the vertical center) and the antisense strand (values extending downwards from the vertical center). The overlayed light-gray density graph shows the average nucleosome density around the same set of transcription start sites.