Mohamed-ali HAKIMI EPIGENETIC AND PARASITES

Course and current status

Born in Algeria, March, 09 - 1974

Status : French-Algerian,  Married, two children.

PAST and CURRENT POSITION

 

• Since 2016 : Head of the Team "Host-pathogen Interactions & Immunity to Infection" (Institut Albert Bonniot, INSERM 1209, CNRS UMR5309, UGA)

•  2004-2015 : Head of the Team "Epigenetic & Parasites" (CNRS / UJF, UMR5163)
 

• Since December 2010 : INSERM Research Director (DR2)

 2004-2010 : INSERM Permanent Scientist (CR1)

 2008 : HDR (Diploma for the capacity to supervise Ph. D. Thesis) / Joseph-Fourier University

•   Post-doctoral training

            2001 - 2003 : Post-Doctoral  fellow in  Breast cancer and chromatin research

             Lab : Dr. Shiekhattar Ramin (Wistar Institute / UPENN, Philadelphia, USA)

EDUCATION

•  1997-2000 : Ph.D in Plant Molecular biology / Joseph-Fourier University (Grenoble, France)

Thesis director :  Dr. Lerbs-Mache S. (CNRS)

• 1995-1996 : Master degree (Laval University, Quebec, CANADA)

OTHER EXPERIENCES

• 1998-2000 : Funder and CEO of Biotechnology for Human development, a French NGO currently involved in a number of water and sanitation projects throughout Africa (Togo and Senegal) to improve living conditions in rural areas.

Since 2010 : Editorial board member at PloS ONE, Molecular Microbiology and Molecular and Biochemical Parasitology.

Referee for the following scientific journals : Nature Microbiology, PloS Biology, PloS Pathogens, PloS One, Molecular and Cellular Biology (MCB), Chemistry & Biology, Molecular Microbiology, Journal of Cellular Biochemistry (JCB), BMC Biology, BMC genomics, Microbes and infection, International Journal for Parasitology (IJP), Journal of Molecular Biology (JMB), Molecular and Biochemical Parasitology (MBP), The International Journal of Biochemistry & Cell Biology, International Journal of Biological Sciences, Cellular Microbiology, Antioxidants & Redox Signaling (ARS), Apoptosis, Trends in Parasitology, Expert Review of Anti-Infective Therapy, Parasitology, Trends in Biochemical Sciences (TIBS).

Past and Present Training Record of Advisor

- Saksouk Nehme, PhD fellow (2003-2005).

- Celine Sautel, PhD fellow (2005-2008), MENRT Scholarship

- Daniele Maubon, PhD fellow (2006-2010) – joint supervision with Pr. Pelloux.

- Jean-Benjamin Murat, PhD fellow (2010-2014) – joint supervision with Pr. Pelloux.

- Fabien SINDIKUBWABO, PhD fellow (2013-…) ParaFrap fellowship

- Céline DARD, PhD fellow (2014-…) – joint supervision with Pr. Pelloux

- Huan HE, PhD fellow (2014-…) – joint supervision with Dr. Bougdour

- Gabrielle GAY, PhD fellow (2015-...)

- Danaya FARHAT, PhD fellow (2016-...)

- Hélène MARCHE, PhD fellow (2016-...)

Awards

- 2000 : Recipient of the young scientist award of Grenoble city

- 2003 : Recipient of « Prix Claude Paoletti » (CNRS award)

- 2014 :  ERC Consolidator Grant (2014-2018)

- 2015 : National Junior Sanofi - Institut Pasteur Award 2015

 

PRESENTATION AND HISTORY OF THE TEAM

https://www.youtube.com/watch?v=AC0HpCif_c0

Starting in 2004, the Team received initial funding under the CNRS Young investigator ATIP-plus (2004-2008) program. Since then, the Team has been hosted in the CNRS/UJF unit UMR5163 (Grenoble). Over the years, we launched fruitful collaborations (e.g. EMBL-Grenoble, ICGEB-New Delhi, MIT-Boston) and gained international recognition for our contribution on epigenetics research and host-parasite interactions in parasitology community using Toxoplasma gondii as a model. The Team was also supported by multiple national funding from the ANR and private foundations (FRM, FINOVI). In 2010, the team has been renewed for five years by the AERES with an A+ grade. The same year, the translational research group headed by Pr. Pelloux (CHU-Grenoble) joined the Team. Together, we were able to achieve seminal in vivo experiments in the mouse model of Toxoplasmosis. In 2013, Dr. Bougdour is laureate of an ANR ”Young Researcher”. In 2012, the Team and 19 leading groups of the French parasitology community were laureate of the LABEX PARAFRAP (Alliance Française contre les Maladies Parasitaires). Following this national recognition of excellence, the European Research Council (ERC) awarded us in 2014 a Consolidator Grant.

Scientific summary

Apicomplexa protozoans form a phylum of obligatory intracellular parasites that contains important human pathogens including the agents of malaria (Plasmodium sp.) and of toxoplasmosis (Toxoplasma gondii). Toxoplasma completes its life cycle by successive processes of parasite differentiation that rely on a tight control of gene expression to ensure appropriate protein profiles on time. Our goal is to  address how epigenetic regulation of gene expression in both parasite and host cell drives the fate of the interaction. Our laboratory has pioneered this field of investigation by identifying and characterizing components of the epigenetic machinery of Toxoplasma, and emphasizing the potential impact of histone modifications. While as for other eukaryotes, the activity state of a gene is determined by a complex regulatory network of co-acting factors affecting the structure of the chromatin in which the gene is embedded, several peculiarities seem unique to the parasite and deserve further mechanistic studies. More recently, our team has also discovered a vast and hitherto hidden repertoire of parasite small RNAs that we now hypothesize as part of the regulatory network governing Toxoplasma differentiation. As a follow-up of our past and current work, we have three distinct but related projects:

i) How histone modifications, small RNAs and a small subset of divergent transcription factors could regulate and coordinate gene expression in Toxoplasma during growth and differentiation thereby determining parasite virulence.

ii) How parasites could interfere with host cell epigenetic pathways, in particular with the microRNA pathway to ensure growth and survival within the host. Specifically, we plan to search for and characterize parasite products that are secreted in the host cells and eventually modulate the host immune response during infection.

iii) How histone deacetylase inhibitors are acting on their parasite targets to initiate the development of selective and sterilising drugs against Toxoplasma as well as potent molecules against malaria.

Our major challenge is to integrate the protozoan Toxoplasma as a new informative «offbeat» model to study the diversity and the evolution of epigenetic machineries and RNA-based processes in eukaryotic cells.

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