The best way to handle the 'Tell me about yourself' question in a job interview, and how to explain a layoff

When asked "Tell me about yourself," skip reciting your résumé and give a short, role-focused pitch that shows you understand the job.
Highlight the most relevant recent experiences (think reverse-chronological) and close by saying why this specific role/company excites you—be memorable, not exhaustive.
If you were laid off, be honest and brief: acknowledge it, emphasize what you learned or did since, and never badmouth your former employer.