science

Apart from my photography, I also take pride in my contributions to science. For those who wish to learn more, I am providing a four-paragraph overview of my past research, along with links to my publications.

In my work as a PhD and Master’s student 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 and we still lack any treatments for clearing Toxoplasma from those affected. As a leading cause for foodborne illness, Toxoplasma can spread via raw and contaminated food, particularly meat. The parasite can also spread through contact with cat feces and through mother-to-child transmission during pregnancy. Typically harmless, Toxoplasma can cause severe disease in both the unborn and in those with weakened immune systems. Indeed, Toxoplasma's toll on global health is substantial and disease control continues to rely largely on preventing transmission to those at risk.

Developing new and potent treatments against Toxoplasma hinges on the availability of effective techniques for investigating its biology at the molecular level. Many such techniques, however, are unavailable for Toxoplasma. I sought to address this need by adapting new gene-editing techniques based on a cutting-edge technology called CRISPR. These techniques have previously been used in a range of organisms and experimental settings, where they have enabled unprecedented advances in cell-biological studies and drug development, thanks to their ease of use and versatility. Recently, CRISPR-based gene-editing techniques have also helped us tremendously in expanding our knowledge and understanding of Toxoplasma biology. Understanding the processes that enable the success of Toxoplasma as a parasite is indeed key to identifying vulnerabilities for the development of new and effective therapies.

As a result of my research, I generated a genome-wide map of promoters, which are the elements in the DNA sequence that regulate gene activity in Toxoplasma. This map of some 7,000 promoters enables the use of a whole range of powerful research techniques, including the gene-editing technique I adapted, called CRISPR interference. With both the promoter map and CRISPR interference, we can now reliably target specific genes and control their activity. This allows us to learn more about the function of individual genes and to evaluate their role as potential targets for therapeutic intervention. In combination, the genome data I created and the technique I adapted may thereby expedite the development of new antiparasitic drugs.

My work, along with many other scientific endeavors, represents but an incremental advance in the study of Toxoplasma biology. Nonetheless, the data I generated and the findings I made are serving as an important resource for many parasitologists around the globe, facilitating current and future projects in elucidating Toxoplasma biology and in mapping out new pathways towards antiparasitic therapy.

CAPTION FOR COVER IMAGE

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.

CO-AUTHORED PUBLICATIONS [click here for Benedikt Markus' publications on Google Scholar]

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


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).


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).


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).


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).


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


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).


* denotes equal contribution