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Frederick Alt ’71 receives 43rd annual Rosenstiel Award for Distinguished Work in the sciences

On Monday afternoon, April 13 in Gerstenzang 123, Frederick Alt ’71 was awarded the 43rd annual Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research. The medallion and accompanying cash prize is awarded to each recipient for their discoveries and contributions to the field of basic medical research. Alt received this award for his work in the mechanisms behind genome rearrangements in immune and cancer cells. He is now the second Brandeis alumnus to earn this award.

Prior to receiving the medallion, Alt presented a lecture on what may be contributing factors to certain patterns of genomic mutations.

Alt described one of the newest methods to detecting these microscopic changes, “… this approach, which we call High Throughput Genome-wide Translocation Sequencing, or HTGTS … it’s a method that we developed seven or eight years ago now and the goal was to be able to identify endogenous double-stranded breaks in the mammalian genome in high-level resolution and also to be able to map how they translocate to other sequences in the genome and what types of processes contribute to that.”

Genetic translocation is the process of one portion at the end of a chromosome completely breaking off and moving to a different chromosome. Alt’s research focused on why these pieces break off and move to only certain other chromosomes.

“The basic method is,” Alt elaborated, “you put a break somewhere in the cell … you induce the break, you let it translocate, and maybe just after a period of a day or two … and then you go through a period of other … more or less standard genomic steps to isolate all the breaks … and then, now we can sequence them … in the lab and then basically get this library of genome-wide translocation junctions.”

“The key is,” Alt stressed, “the nucleotide-level resolution. You can use it for all sorts of different assays.”

Nucleotides are the basic building blocks of genetic material while an assay is a type of test that identifies which nucleotides are present in specific locations at each location or locus.

Alt told the story of how a colleague discovered that an enzyme “worked by just converting G’s [guanine nitrogenous bases] to C’s [cytosine nitrogenous bases] in DNA, and that turns on a change of downstream events that make the breaks and mutations.”

In a recently published paper, Alt looked at how this enzyme, AID, causes translocations and activates oncogenes. Oncogenes are genes that have the potential to cause cancer. “The most important [study] that we’ve done in collaboration with … UMass,” Alt continued. “What we did there was take progenitor B Cells [a type of white blood cell] … introduced breaks and then looked at how they translocated across the genome … to ask how the organization of the genome … influences how breaks within translocate other sequences.”

“The basic things that came out,” he summarized, “is that if you have very high frequency double strand breaks, they can drive translocations wherever they are. It used to be thought that genes were organized in domains, and the chromosomes here, there, don’t really communicate or translocate with each other. The actual fact is that … in most sequences at least, some small fraction of the cells are in communication with each other and because of that, if you have breaks that are frequent enough, it will drive recurrent translocation…”

Normally, translocation mutations only occur in parts of the chromosome that are not vital to the survival of the organism. Additionally, cells do have some mechanisms in place to correct mutations. However, this research is significant because of the concern that these translocation mutations will result in cancer.

Alt will be continuing his research at Harvard Medical School, where he is a professor of genetics as well as at Boston Children’s Hospital where he is Charles A. Janeway Professor of pediatrics.


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