Research Area: Computational Biology

Biophysicist Ibrahim Cissé and cell biologist Gene-Wei Li honored as Pew Scholars; postdocs Ana Fiszbein and María Inda are named Pew Latin American Fellows.

Julia C. Keller | School of Science

June 20, 2017

The Pew Charitable Trusts has named Ibrahim Cissé, assistant professor of physics, and Gene-Wei Li, assistant professor of biology, as 2017 Pew Scholars in the Biomedical Sciences. In addition, two postdocs, Ana Fiszbein and María E. Inda, were named to the 2017 class of Pew Latin American Fellows in the Biomedical Sciences in computational biology and synthetic biology, respectively.

The Pew Scholars program encourages early-career scientists to pursue innovative research to advance the understanding of human biology and disease. This year, 22 Pew Scholars will receive $240,000 over four years and gain inclusion into a select community of scientists that includes three Nobel Prize winners, five MacArthur Fellows, and five recipients of the Albert Lasker Medical Research Award. The applicants, who conduct research in all areas of biomedical sciences, must be nominated by one of 180 invited institutions. To date, the program has invested in more than 900 scholars.

“Pew’s biomedical programs not only provide young scientists with the flexibility to pursue creative ideas; they also spark interdisciplinary thinking and collaborations that can open new paths in the search for answers,” says Craig C. Mello, who won the 2006 Nobel Prize for physiology or medicine, was a 1995 Pew Scholar, and chairs the Pew Scholars National Advisory Committee.

Cissé, the MIT Class of 1922 Career Development Assistant Professor, says “support from Pew at an early stage is great encouragement in pushing my lab further at the frontiers of different fields.”

Cissé’s research group is investigating the fundamental processes involved in gene activation. Using a combination of techniques in cell and molecular biology, biochemistry, genomics, and super-resolution microscopy, he will continue his investigations of the behaviors of the enzyme involved in the transcription of DNA to RNA molecules. The enzyme, RNA polymerase II, has been well-studied in vitro, but Cissé’s work looks at these transient biological interactions within living cells. His findings will deepen the understanding of these processes, disruptions in which are linked to human disease, including most cancers.

Li’s research looks at evolution of cells’ production of proteins to answer a fundamental biological question of how cells specify how much of each type of protein to produce. In Li’s Quantitative Biology Lab, researchers have developed a technique for measuring the precise production rates of every protein in a cell. Combining this approach with other techniques in cell, molecular, and computational biology, Li is comparing a broad range of organisms across evolutionary distances to determine whether all of their proteins are maintained at some preferred level. By artificially perturbing the quantities of selected proteins, Li can explore the mechanisms cells use to reestablish the proper protein balance to better understand when misregulation occurs that leads to disease.

“The success of my research hinges on close integration between expertise in biological and physical sciences, as well as constant stimulation from both disciplines,” says Li, the Helen Sizer Career Development Assistant Professor. “The Pew scholarship will also provide a unique opportunity to interact with the brightest young minds in the biomedical sciences outside my field that will elevate my research to unanticipated levels.”

Each year, current scholars come together to discuss their research and learn from peers in fields outside of their own. “I am looking forward to interacting with other Pew scholars, many of whom are also working on paradigm-shifting ideas,” says Cissé.

Rebecca W. Rimel, president and CEO of The Pew Charitable Trusts calls the scholars an “impressive group” that has demonstrated “the curiosity and courage that drive great scientific advances, and we are excited to help them fulfill their potential.”

The Pew Latin American Fellows program, meanwhile, is intended to support postdocs from Latin America. Winners are awarded two years of funding to conduct research at laboratories and academic institutions in the United States.

The program also provides additional funding to awardees who return to Latin America to launch their own research labs after the completion of their fellowships. About 70 percent of program participants have taken advantage of this incentive and are conducting work on regional and global health challenges in nine Latin American countries, according to The Pew Charitable Trusts.

“Almost 150 young scientists have returned to their home countries and established independent research labs, providing critical groundwork for biomedical research across Latin America,” says Torsten N. Wiesel, the 1981 Nobel laureate in physiology or medicine and chair of the Latin American Fellows National Advisory Committee.

Ten Pew Latin American Fellows were named this year. The fellowship provides a $30,000 salary stipend to support two years of research, as well as an additional $35,000 for laboratory equipment should the fellow return to Latin America to start his or her own lab. Since the program’s inception in 1990, the program has supported almost 150 young Latin American scientists.

Ana Fiszbein is a postdoc working in the Burge Lab, where she researches the role that changes in gene splicing could play in the biology of normal and tumor cells, with the goal of revealing novel targets for cancer therapeutics. “I am very honored to receive this award, it is a privilege and also a responsibility,” she says. Fiszbein is working with Professor Christopher B. Burge, of the departments of Biology and Biological Engineering and the Broad Institute of MIT and Harvard.

“Ana is an exceptionally talented molecular biologist and independent thinker who came to my lab very well trained from her PhD in Alberto Kornblihtt’s lab,” Burge says. “She has developed very interesting hypotheses about the mechanistic connections between transcription and RNA splicing.”

The activity of genes can be regulated on many levels, including how often DNA is read to produce an RNA, where within the gene that reading begins, and which of the gene’s segments are represented in the RNA molecules that ultimately direct the formation of protein. Tumor cells harbor genetic changes that can alter all three of these points of control. However, little is known about the control of these regulatory processes or how they might be interconnected. Fiszbein is working on a sequence study of RNA in different species, with a sequence analysis of human cancer genomes to identify RNAs that may be present more often in cancer cells. She will then assess whether those RNA segments are co-regulated with the sites where the reading of a gene begins.

Inda is a postdoc working in the lab of Timothy Lu, an assistant professor leading the Synthetic Biology Group in the departments of Electrical Engineering and Computer Science and Biological Engineering. In the Lu Lab, she will work on the development of novel noninvasive strategies, for the early diagnosis and alleviation of inflammation in intestinal disorders, such as inflammatory bowel disease (IBD).

“The fellowship provides me a unique opportunity to learn the practical and theoretical underpinnings of cutting-edge research in the synthetic biology field for diagnosis and treatment of serious ailments,” she says.

A variety of bacteria inhabit healthy human intestines, and members of the Lu laboratory have been working to commandeer some of these microbes for use as sentinels that could patrol the gut and secrete therapeutic molecules in areas that appear inflamed. Inda plans to equip bacteria with biosensors that recognize the molecular markers of IBD — and then trigger the release of anti-inflammatory compounds. She will then assess the engineered microbes’ ability to distinguish between diseased and healthy tissue and to treat inflammation in an animal model of IBD.

Wiesel has high praise for the quality of this year’s Latin American Scholars. “The 2017 class is again made up of researchers of outstanding promise who will no doubt continue to enhance the growing biomedical research community in the region,” he says.

May 4, 2016

Gene-Wei Li is the newest member of the MIT Department of Biology. He opened his lab on the second floor in building 68 about one year ago. But who is Gene? Born in California and raised in Taiwan, Gene fell in love with math and physics and a boyhood dream to figure out quantum teleportation. It was not until he arrived at Harvard that he discovered the field of biophysics. “As a physicist I like thinking about numbers and when I came to Harvard I suddenly realized there was so much biophysics going on in a diversity of labs,” Gene says of his years in graduate school.

In his thesis project, Gene was looking at how transcription factors find their target through single molecule imaging in bacterial cells. He became focused on protein dynamics. Do transcription factors diffuse through cytosol and randomly land on DNA or do they scan through in a directional manner? He discovered they do a bit of both. “As a cell you would optimize the amount of transcription factors searching at any given time and the number of sites. You would not want to crowd the DNA,” Gene explains smiling.

Despite his work in a biological system, Gene admits he still saw himself primarily as a physicist at the beginning of his postdoc. “When I started my postdoc at the Weissman lab at UCSF, I did not even know what ubiquitin was,” he laughs. That was soon to change. At UCSF, Gene utilized a novel method called ribosome profiling which enables the study of protein synthesis rates by looking at ribosome density. “In my postdoc, I was lucky to get a paper published early on and so I had an opportunity to explore what I enjoyed. Quantification is always hard so I decided to see whether there is a good metric to measure, and found a striking result that density corresponds to stoichiometry really well. All the subunits are made in proportion to their stoichiometry. While this makes intuitive sense it was not necessarily obvious before,” Gene describes his postdoctoral experience. What about single subunit proteins? “No protein acts alone,” Gene replies, “we need to look at a whole system — enzymes could be diffusing but receive substrates and the amount of enzyme matters. Make enough but not too much because that would be wasteful.”

Are there physical and quantitative principles behind the precise control of transcription and translation? How do cells fine-tune their RNA and protein production to result in correct stoichiometric complexes? And importantly, if a cell is engineered in the lab to express exogenous proteins are there detrimental effects? Gene’s growing team at MIT (currently, two graduate students, a technician, an undergraduate, and a joint postdoc) are focused on cracking precisely these key questions. “As a mentor, my philosophy is to be supportive but leave freedom for students and postdocs to explore on their own too. In graduate school, I was stuck on a project for two years but was also allowed to follow side stories that both eventually went to fruition.”

Gene’s lab uses bacteria (E.coli and B. subtilis) in their experimental work. “Their operons are surprisingly conserved despite a billion years’ separation. The power is in comparison though – even though the gene order and protein stoichiometry are conserved, these bugs use different tricks of post-transcriptional controls to get the same amount of proteins,” Gene says of his model organisms. Being a young faculty in the MIT Department of Biology is a very humbling experience because it has so much history, he adds. “Boris Magasanik from this department was one of the pioneers of bacterial physiology — we know the system much better now, we can quantitate it better too but he laid the foundation. My lab space is formerly Alexander Rich’s who discovered polysomes — now we are stretching polysomes individually and looking at the actual distribution of ribosomes along the mRNA.”

In his free time, Gene enjoys traveling with his wife though it has become more difficult with the recent birth of their son (congratulations!) and his three-year old brother. He loves meeting people of different backgrounds and thinking about science from different perspectives. “It takes a while to adjust from postdoc to faculty – becoming a manager, accountant, grant writer, colleague, mentor – leaving less time for research,” he says. “The nice thing about the MIT Biology Department is that I can knock on any door and ask for advice on things big and small.”