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Alessandro Datti
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Alessandro Datti

Alessandro Datti
by Sophie Lily Polan

 

alessandro dattiAlessandro is a biochemist with a particular expertise in assay development for high throughput screening (HTS) and has been at the Lunenfeld-Tanenbaum Research Institute (LTRI) for the past 14 years. He is also a senior lecturer of Biochemistry and Molecular Biology with an Italian University. In the past, from 1996 until 2003, Alessandro had worked as a Senior Scientist/Project Leader of a Toronto biotech company (Glycodesign Inc.), where, together with his supervisor, Dr. Jim Dennis of the LTRI, pioneered high throughput screening aimed at the discovery of novel pharmaceutical entities. This biotech experience was subsequently transferred to the LTRI in his current role of manager of the SMART Laboratory for High-Throughput Screening Programs. Over his tenure at the LTRI, he’s actively contributed to the Facility grow in terms of space, machines, investments and success stories. The HTS lab runs as an operational and training facility that is open to the scientific community, either local or external, to make use of the machines and the key reagents purposely assembled for the application of the widest variety of screening programs. In this regard, there are three components to Alessandro’s work: novel drug development, drug repositioning and functional genomics.


The first theme of Alessandro’s work is novel drug development, which uses libraries of small molecule chemicals to identify possible new drugs. The lab has more than 220 thousand chemicals that are used to identify functional effects on cells with a potentially pharmacological impact. Due to the large number of chemicals there is an incredibly large number of assays to be done, so there is an automated robotics machine that is able to test each chemical – typically in parallel using 384 well or 1536 well plates. To start, a screen must be developed to identify the appropriate molecular target - which is typically a protein. While most researchers are used to testing a handful of conditions, in HTS the numbers of assays to be performed mean that there is usually a substantial period of assay development to convert the initial test into a reliable, cost-effective assay that can be efficiently measured. This is often the hardest part of the process as scaling up is not trivial. Another similarly challenging aspect is data analysis as current screens generate enormous amounts of data that must be rigorously filtered to reduce noise and systematic errors. This expertise is a valuable asset in the HTS group.


The second role in Alessandro’s portfolio makes use of the fact that few drugs are totally specific in their targeting. Most drugs have “off target effects” that interfere with the function of proteins unrelated to their intended purpose. This can be the cause of adverse or side effects when taking a drug. Drug repositioning takes a known drug that is used for a specific purpose and reassessed for use in a distinct therapeutic application. This begins with a biological question such as a need for more effective therapies for certain cancers, such as leukaemia. The next step is to develop an assay evaluate whether a compound can differentially kill leukemia cells but leave normal cells intact. One screen in the laboratory discovered an antifungal reagent was also selectively active on certain leukemia cells. This is one of the five big success stories from the lab that went on to testing in clinical trials. It turned out that was a biological process shared between fungi and leukemia cells which allowed the drug to be repositioned , thereby leading to a different usage.

 

alessandro datti-.jpgThe last aspect of screening that Alessandro and the HTS Lab personnel perform is functional genomics. This is about learning what a gene does in a cell and the impact of manipulating that gene on a given system. The goal is to identify, in a systematic manner, the functions of genes by blocking their expression by means of siRNA (short interference RNA) or CRISPR guide RNAs. siRNA screening involves silencing specific genes, one at a time, and observing the effect of that change in the cells. The effects of siRNAs may be manifested through altered growth rates, induction of cell death/ apoptosis or even changes in shape (morphology) or cell motility. Collection of this type of data allows understanding of what cellular processes the gene may influence, thus adding to knowledge about the gene as well as its potential as a therapeutic target. This is one impact big data is having on biomedical research.

 

Going forward, Alessandro sees this area moving in two directions: improvements in assay development/identification of novel molecular targets for drug discovery and greater emphasis on mechanistic studies – due to the efficiency of new screening capabilities. A goal of Alessandro’s is not only to identify new drugs but to help the academic community move their research forward. The lab has repositioned itself to act as a bridge to help other researchers, at the LTRI and elsewhere, to translate their basic science discoveries into possible new drugs.

 alessandro datti---.jpg alessandro datti--.jpg

 

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