Alberto Kornblihtt

Alberto Kornblihtt (born June 30, 1954) is an Argentine molecular biologist who specializes in alternative ribonucleic acid splicing. During his postdoctoral training with Francisco Baralle in Oxford, Kornblihtt documented one of the first cases of alternative splicing, explaining how a single transcribed gene can generate multiple protein variants. Kornblihtt was elected as a foreign associate of the National Academy of Sciences of the United States in 2011, received the Diamond Award for the most relevant scientist of Argentina of the decade, alongside physicist Juan Martin Maldacena, in 2013,

Early life and education Alberto Kornblihtt was born on June 30, 1954, in Buenos Aires, Argentina. was alternatively spliced and could result in the generation of twenty polypeptides.

Research After completing his postdoctoral research in Oxford, Kornblihtt returned to Argentina in 1984 and accepted a position as an assistant professor of molecular and cell biology at Facultad de Ciencias Exactas y Naturales at the University of Buenos Aires. In 1991 he was appointed full professor and at present he is professor emeritus. Kornblihtt is also a senior CONICET investigator of the CONICET and works with a research team to study the regulation of alternative ribonucleic acid splicing. Alternative splicing occurs during gene expression, allowing exons from a gene to be excluded or included, resulting in a single gene generating multiple proteins. Major projects in Kornblihtt's lab focus on: 1) Coupling transcription with alternative splicing; 2) Alternative splicing and Chromatin; 3) Alternative splicing and spinal muscular atrophy; 4) Ultraviolet light irradiation and alternative splicing; and 5) Alternative splicing in plants.

Research on coupling transcription with alternative splicing Kornblihtt's lab focuses on the mechanisms that couple transcription with alternative splicing for the regulation of alternative pre-mRNA splicing. Transcription is the process in which a genetic sequence of a gene is transcribed, or changed, from DNA into RNA, to allow for protein production. One of the most significant accomplishments in Kornblihtt's research came in 1997. Kornblihtt's research team was able to an alternative splicing assay combined with promoter swapping to demonstrate that transcription promoters affect the outcome of splicing They later determined that the coupling of transcription and splicing is dependent upon transcriptional elongation speed, or kinetic coupling, and the impact of transcribing RNA polymerase II on splicing. Kornblihtt's research has found that elongation affects alternative splicing events, with slow elongation increasing inclusion of approximately 80% of exons and skipping of approximately 20% in mammalian cells.

More on alternative splicing and chromatin An additional area of Kornblihtt's study investigated the impact of chromatin structure on alternative splicing. Kornblihtt's research team demonstrated that alternative splicing is impacted by chromatin structure and the rate of transcription. They found that a tighter chromatin structure provides lower rates of elongation and looser chromatin structures provide a higher rate of elongation of transcription. This is due to the deletion or mutation of Survival of Motor Neuron 1 (SMN1). Due to the faulty SMN1 gene, SMA patients do not have enough SMN protein. SMA patients must depend on Survivor of Motor Neurons 2 (SMN2), a gene that all humans have. SMN2 cannot produce sufficient full-length protein for the motor neurons to signal muscles due to sequence differences and the exclusion of exon 7, resulting in the overall SMN protein deficiency. Spinraza is an oligonucleotide that works to activate SMN2 to make more SMN protein in SMA patients. In 2015, the families of Spinal Muscular Atrophy patients encouraged Kornblihtt and Krainer to work together to improve the effectiveness of Spinraza or to develop alternative therapies to be used in conjunction with Spinraza. Kornblihtt's research team focuses on epigenetic strategies, a different mechanism than used Spinraza, to increase SMN protein from the SMN2 gene. Epigenetics studies changes in gene expression, without alteration to the DNA sequence. In 2017 and 2019, Kornblihtt received three separate grants from CURE SMA and FAME (Families of SMA, Argentina) to support continued work on his projects "Epigenetics in SMN2 E7 Alternative Splicing" and "Epigenetics in SMN2 E7 Alternative Splicing II". In these projects, Kornblihtt's team has worked on the regulation of alternative pre-mRNA splicing to develop new mechanisms for SMN protein development, using a single gene to generate multiple proteins.

Alternative splicing in plants Adding to their research performed on human cells, Kornblihtt's team expanded their research to study transcription and alternative splicing in plants. The plant Arabidopsis thaliana was used to investigate how external lighting conditions affected alternative splicing. Research showed that the chloroplast, where photosynthesis occurs, senses light and sends a signal to the cell nucleus to regulate alternative splicing. As previously found in mammalian cells, Kornblihtt's team demonstrated that alternative splicing in plants responds to the kinetic coupling mechanism. Their research further showed that light promotes elongation in RNA polymerase II (Pol II) while elongation is lowered in darkness.

Honors and awards In 1991, Kornblihtt received the Guggenheim Memorial Foundation Fellowship in Natural Sciences, awarded on the basis of previous achievement and basis of prior achievement and outstanding promise. Between 2002 and 2017, Kornblihtt received the International Research Scholar of the Howard Hughes Medical Institute (HHMI) Award, given to scientists outside of the United States who have notably contributed to biological science research. In 2003 and 2013, Kornblihtt was the recipient of the Konex Platinum Award, a cultural award given to Argentines in different fields of work. In 2012, Kornblihtt was elected foreign member of EMBO (European Molecular Biology Organization). In 2013, Kornblihtt was a recipient of the Diamond Award for the most relevant scientist of Argentina of the decade, alongside physicist Juan Martin Maldacena. In 2022, Kornblihtt was elected as foreign member of the Académie de Sciences of France. Kornblihitt is a three-time recipient of the CURE SMA and FAME Grant in 2017, 2019 and 2023 for his research projects, Epigenetics in SMN2 E7 Alternative Splicing" and "Epigenetics in SMN2 E7 Alternative Splicing II".